|
Asante
Omnicyclion prophet
Registered: 02/06/02
Posts: 87,282
|
Memantine -dissociative entheogenic pharm [Alzheimer's]
#3033547 - 08/21/04 05:27 PM (19 years, 7 months ago) |
|
|
Guys.. I'm placing our little ODD thread-jack into a thread of its own, in Sci/Tech where it belongs as we're dealing with a new class of medicinal pharmaceuticals, quite revolutionary, as wel as being the first daily pharmaceutical that is a dissociative entheogen based on the NMDA antagonist mechanism shared by substances such as Nitrous Oxide, PCP, Ketamine, DXM and Tiletamine. WARNING: NMDA antagonists (N-Methyl-D-Aspartate inhibiting substances) generally carry substantial abuse potential and a risk of irreversible brain damage, even if, in correct usage, they may actually protect neurons from harms as diverse as neurotoxicity, hypoxia and appears to stall neural degeneration as in Alzheimer's disease.
Quote:
Aneglakya said Have you ever heard of Menantine HCL.. Its suppost to be the next Caffiene/Amphetamine... The Entheogen Review recently posted a bunch of information on it. It sounds really amazing and has a very long half life, also significantly changes the metabolism of other drugs. Randolph Carter (НơĻ? ĢΉōsŧ) 08/21/04 10:46 AM Re: 4oz. Of Pure Caffine Powder No, i hadn't heard of that......links? Is it supposedly of interest as an illicit stimulant? Any synth discussion as of yet? And what the bloody hell does your name mean? Aneglakya (mephitic conjurator) 08/21/04 12:42 PM Re: 4oz. Of Pure Caffine Powder Thats about all I know about it (Manentine hcl). I'll see if I can find some more information. I believe you need a prescription but according to these reports its going to be a pretty big deal when its made more readily available. I dont even know what class of chemicals it is in. Its supposebly pretty expensive too. Also, it is said to increase the effects of hallucinogens like psilocybin and ketamine A LOT as well as lower the effects of opiates such as morphine. GET The newest edition of The Entheogen Review.. its only a few bucks and it is simply the best underground mag dealing with phytopharmacology and clandestine psychedelics.. Psiloman (member) 08/21/04 05:34 PM Re: 4oz. Of Pure Caffine Powder Excuse me if i am wrong but i think you are reffering to MEMANTINE. Have a look at this url http://www.alzheimer.ca/cgi-bin/care-arc...3473-003452.msg And this url http://www.memantine.com/en/ Aneglakya (mephitic conjurator) 08/21/04 05:56 PM Re: 4oz. Of Pure Caffine Powder welll.. I dont have my ER copy with me or I would check the spelling but I was sure they spelled it Menantine hydrochloride.. I'll check again when i get home. Wiccan_Seeker (ex-addict since dec '02) 08/21/04 10:01 PM Re: 4oz. Of Pure Caffine Powder Wow! Memantine had an adamantane sound to it and indeed its a funky dimethyl derivative thereof chemically. Adamantane, the "parent" is a direct dopamine agonist. Well.. thats an interesting pot these pretty-looking molecules are stirring in. But this is Memantine.. it is an NMDA Antagonist. Memantine, being the first therapeutically applicable member of its class, will likely be the parent compounds of one of the greater pharmacological revolutions to date, In my view it might be as great a discovery as that of the Antidepressants, as it has healing potential that lies far beyond its currend indicated spectrum, and this and more selective analogs might save millions of lives in the years to come as it can prevent all sorts of neuron/brain damage, which in for instance the surgical operating room might translate to one injection of Memantine or a future analog might make the difference between a healthy and a heavily braindamaged one should a mishap occur. This NMDA-antagonism also means it is a dissociative akin to nitrous oxide, PCP, DXM and Ketamine that actually made into the daily use as apharmaceutical. Indeed its most prominent "side effect" (bullshit) consists of "hallucinations", no shit Sherlock! THey try to warm the doctors up to NMDA antagonists on the pharm website. -great news- because the NMDA antagonists hold great promise as medicines AND visionary psychoactives. Likely a full medical dose (5-20mg as is recommended as maintenance therapy for alzheimer patients after the visionary components are nixed, if taken as a first (and only) dose will be pretty visionary behind closed eyelids. Remember sales politics are in action, so the scientific statement of 2% side effects should likely be read as: "if daily treatment of slowly rising low dosages is followed it will through tolerance eliminate psychological side effects (visionary etc) in the vast majority of patients" If it applied they would rather not say that a higher initial dosage may cause a vivid hallucinatory syndrome, a bit akin to the homeshopping network saying "it is such a good chrome knob-polishing wax that you should keep it away from the kids!" instead of "If your toddler drinks from the chrome-cleaner bottle he'll die a slow agonizing death over the course of five days" Same with pharmaceuticals: if you insist on gradually introducing a drug you likely want to decrease some side effects or other reactions, and the side-effects look like those of an NMDA antagonist with "hallucinations" being the first mentioned. A little example of pharmaceutical "scientific" drug politics.. This first brief summary is from the multinational pharmaceutical company Quote: -------------------------------------------------------------------------------- Common adverse reactions (1 - 10% and more frequent than with placebo) for memantine and placebo patients respectively were: hallucinations (2.0 vs. 0.7%), confusion (1.3 vs. 0.3%), dizziness (1.7 vs. 1.0%), headache (1.7 vs. 1.4%) and tiredness (1.0 vs. 0.3%). Uncommon adverse reactions (0.1 - 1% and more frequent than with placebo) were anxiety, hypertonia (increased muscle tone), vomiting, cystitis and increased libido. Based on spontaneous reports, seizures have been reported, mostly in patients with a history of convulsions. 4.9 Overdose In one case of suicidal overdosage the patient survived the oral intake of up to 400 mg memantine with effects on the central nervous system (e. g. restlessness, psychosis, visual hallucinations, proconvulsiveness, somnolence, stupor and unconsciousness) which resolved without permanent sequelae. Treatment of overdosage should be symptomatic. -------------------------------------------------------------------------------- Now compare this with the second, larger, list of side effects from a US gov't sponsored general medical website: Quote: -------------------------------------------------------------------------------- Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention. Check with your doctor immediately if any of the following side effects occur: Less common Bloating or swelling of face, arms, hands, lower legs, or feet ; blurred vision; dizziness ; headache; nervousness ; pounding in the ears; rapid weight gain; slow or fast heartbeat; tingling of hands or feet; unusual weight gain or loss Other side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. However, check with your doctor if any of the following side effects continue or are bothersome. More Common Confusion Less common Anxiety; back pain; bladder pain; bloody or cloudy urine; change in walking and balance; chills ; clumsiness or unsteadiness; cough producing mucus; coughing; difficult, burning, or painful urination; difficulty breathing; difficulty moving; difficulty having a bowel movement (stool); diarrhea ; discouragement; dry mouth ; fear; feeling sad or empty ; fever; frequent urge to urinate; general feeling of discomfort or illness ; hyperventilation; insomnia ; irregular heartbeats; irritability; joint pain; loss of appetite; loss of bladder control; loss of interest or pleasure; lower back or side pain; muscle pain or stiffness; nausea; nervousness; pain; pain in joints; restlessness ; seeing, hearing, or feeling things that are not there; shortness of breath; sleepiness or unusual drowsiness; sore throat; tightness in chest; tiredness; trouble concentrating; trouble sleeping ; unusual tiredness or weakness; vomiting; wheezing P Other side effects not listed above may also occur in some patients. If you notice any other effects, check with your doctor. -------------------------------------------------------------------------------- Notice? The pharmaceutical company lays emphasis on the psychological side effects. They likely see that these mostly need tender loving care which any Alzheimer patient does, until the side effects have worn off. The US gov't sponsored site however barely hints at the major initial side effect (NMDA antagonist psychoactivity) but instead they present it as if it were a poison from hell, greatly upsetting patients and their relatives and perhaps causing their doctors to freak when their rare patient closes his/her eyes and dances with Tutanchamon and recites the runes from the sarcophagus. True: both are right. But the predominant side effects according to the manufacturer are mainly psychological (think sweet loving care of relatives and understanding nurses bearing Valium and reassuring words) which i believe, but the US gov't sponsored site elaborates on every possible thing BUT the above and scares relatives who think granny has gotten poisoned and gone insane and doctors running around in a panic mistaking it for toxic delirium, while in fact anti-NMDA psychotropic effect is relatively benign. The company with the real experts comes clean on the psychotropic part that some patients might encounter. The US gov't site seems a wee bit to play the part of a WOD warrior at the expense of basic trust of medical personnel, relatives and most importantly the patients. If the bodyload is relatively and statistically benign, which likely is the case, I deem in the light of Alzheimer-progression slowing effects a controlled state of anti-NMDA dissociative syndrome in a few patients for the startup time more than worth the unpleasantness of the altered states that can be managed with gradual upping of doses, love, understanding and Xanax of informed relatives and medical personnel. Bluntly said: a week or so of a controlled dissociative anti-NMDA "high" might well be a pleasant temporary lulling of Alzheimer's anguish if it is handled well. Drug science vs Drug politics.. note the difference? It both is sound science but the hidden political agendas make them into two entirely different reads... No matter how one chooses to present it: It will likely have abuse potential and it's NMDA antagonist profile makes it suspect for detrimental long-term effects (remember its for alzheimer patients and risk/benefit is weighed against that horrible brain degeneration syndrome, not a healthy functional person.) But also it will be one of the purest Visionary compounds in the pharmaceutical arsenal. Its risks and benefits possibly outclass those of Ketamine as its a modern day-to-day oral pharmaceutical. I do not recommend any psychoactives and i am very weary of the dissociatives, but i notice that modern medicine accepts it as a viable pharmaceutical. I want to discourage Memantine's non-prescription use as it may hamper the pharmacological revolution. However it will, like anything under the sun, be diverted by many to see if it "does anything" so since it likely does this hampering will occur with statistic certainty. It really belongs in a doctor's hands as it is potent medicine which like any pharmaceuticals will be harmful to some. If one were not an alzheimer patient, an if one's doctor prescribed it for incidental use I would say bi-monthly to seasonal use (4-6 x a year) would likely be the upper limit of frequency for entheogenic doses, which likely are found in the higher medical dose range of the compound as a single dose without boosting. Again, I strongly disrecommend any non-prescription use, but a single moderate to high medical dose (without visionary tolerance) spaced months apart in practice proves to be workable for users of for instance Ketamine, Mushrooms or LSD. The NMDA-antagonist closed-eye visions will likely be very involving and have potential for overwhelming dreamlike states akin to PCP or its close analog Ketamine. Memantine: pretty potent stuff, especially as a novel pharmaceutical with the NMDA-antagonist promise it holds for improved analogs that may save millions of lives in the long run. Randolph Carter (НơĻ? ĢΉōsŧ) 08/21/04 10:37 PM Re: 4oz. Of Pure Caffine Powder that looks like it'd be a bitch to make..... substituted adamantines are just ugly to begin with (not structurally, but from the viewpoint of inducing additions....you get my point) nice write up tho, wiccan..... Were you aware that some of the adamantine compounds also show serious potential as anti-viral agents? Indeed they'er some of the only effective ones known to date... How long till we see somene with an elderly relative post about this? Wiccan_Seeker (ex-addict since dec '02) 08/21/04 11:58 PM Re: 4oz. Of Pure Caffine Powder LOL even the parent compound (ex the two methyls, just the beeeeautiful alkylamine) has that antiviral activity, together with its Dopamine spike. That must make an interesting bedside consultation.. "And Miss Woodrow.. how are we feeling today?" "DOCICANTBELIEVEITIFEELSOF#CKINGGOODICOULD *breathes* HOLAHOOPOHMYGODDOCTORYOUHAVECUREDTHINGSIDIDNTKNOWIHAD !" "You.. seem a bit excited.. Perhaps we should discontinue.." "SWEETMOTHEROFSH#TSTAYTHEFUCKAWAYFROMMEIWILLBEATYOUTODEATHWITHMYBEDPAN *breathes* UPTHEDOSAGEYOUBASTARDORIWILLSTABYOUWITHMYIVNEEDLE !" Well as for this one it seems pretty straightforward Adamantane + 2 Li-R --> Adamantane di-lithium ADL + 2 CH3-X --> Dimethyl Adamantane (two isomers, both are tert and fractionally distillable to yield the right DIMA) DIMA + Br2 --catalysis--> Bromodimethyladamantane (same story) Br-DIMA + NH3 --> Memantine HBr This is just top of the head stuff.. (1+2 may need repeat to go to dimethyl through monomethyl) if chemistry was this easy. Its just crossword-puzzling, nothing like the real boys are doing NMDA antagonists majorly get my goat as for curative medicinal purposes.. Finally we opened up a new class, and one as big as the Neuroleptic revolution as dire stuff as of yet untreatable will now be either slowed in degeneration (Alzheimer), halted (other neurological syndromes that pass with time) or even entirely prevented (neurologic damage in emergencies) If someone can post personal experiences with a relative struck by Alzheimer who is on Memantine we'd really like to know. Sometimes "high" means "less ill" Randolph Carter (НơĻ? ĢΉōsŧ) 08/22/04 12:28 AM Re: 4oz. Of Pure Caffine Powder Yeah, ity seems straight forward, but the adamantine doesn't have anywhere near the same stability an aromatic would....i'd be all sorts of worried about breaking it up, and substituting at the wrong positions... I dunno, it just seems like it'd be nasty. didn't know about the dopamine spike tho.... If i find anythign interesting regarding the chemistry, i'll drop a copy here. Wiccan_Seeker (ex-addict since dec '02) 08/22/04 01:11 AM Re: 4oz. Of Pure Caffine Powder It looks like a pretty solid piece of LEGO But indeed, he-man alkaline bases like simple alkyllithiums have got a way of rearranging even a pretty honycomb ball like this one. The substitutions would hardly be a prob: you've got only sec- and tertiary carbons so the lithiums will reattach until they got solid tertiary to hold onto (most active) Once the methyls are in place you got all types. the terts with the methyls become all-carbon bonded so they are out of there. I recall bromine in the presence of UV light will very selectively attach to R3C-H + Br-Br --UV--> R3C-Br + HBr but if not there got to be ways to separate em, and otherwise its a matter of cooking off the stuff thats put together wrongly through destillation. Interesting is how the Dopamine ties into the NMDA-antagonists. Things like psychosis and increased libido suggest there might be some dopaminergic side-effects. Unfortunately Dopamine tends to get kids into trouble; meth, ritalin, cocaine.. bad stuff. The paper I quoted mentioned the fact that Olney's Lesions (brain damage) were observed in wrong , to be expected, i think quite avoidable, but horrid in abuse situations... THREADJACK!!! Say we're majorly jacking the caffeine thread and pollute it with all this discussion so I'll C&P it into a Memantine thread of its own! Aneglakya (mephitic conjurator) 08/22/04 01:11 AM Re: 4oz. Of Pure Caffine Powder Does someone care to make a fresh memantine post? I think this chemical is Deff. worth active discussion. Wiccan, maybe you can start it up and transfer that information over because I am ready to start actively pursing research on this material. so are psiloman and I talking about the same chemical?
.
Edited by Asante (08/21/04 05:54 PM)
|
Asante
Omnicyclion prophet
Registered: 02/06/02
Posts: 87,282
|
Re: Memantine -dissociative entheogenic pharm [Alzheimer's] *DELETED* [Re: Asante]
#3033554 - 08/21/04 05:30 PM (19 years, 7 months ago) |
|
|
Here is the entire article from MERZ Pharmaceuticals GmbH. Since pharmaceutical companiestyend to only volunteer the stuff required by the law of the land, I also read the German version to see if any scheisse was witheld from us. They're on the level. Yopu can find the neat .pdf file HERE but it requires Adobe Acrobat(Reader) or if you want true freedom from the Hells of Software pricings you can get OPEN OFFICE which does everything with .pdf and .doc and far more then you ever dreamed of, totally legit at no charge! For those who'd rather not, here's the text from the Pharm Co.
Quote:
1 SUMMARY OF PRODUCT CHARACTERISTICS 2 1. NAME OF THE MEDICINAL PRODUCT Axura 10 mg film-coated tablets. 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Each tablet contains 10 mg of memantine hydrochloride (equivalent to 8.31 mg memantine). For excipients, see section 6.1. 3. PHARMACEUTICAL FORM Film-coated tablets. The film-coated tablets are white to off-white, centrally tapered oblong, biconvex, with a single breakline on both sides. 4. CLINICAL PARTICULARS 4.1 Therapeutic indications Treatment of patients with moderately severe to severe Alzheimer?s disease. 4.2 Posology and method of administration Treatment should be initiated and supervised by a physician experienced in the diagnosis and treatment of Alzheimer?s dementia. Therapy should only be started if a caregiver is available who will regularly monitor drug intake by the patient. Diagnosis should be made according to current guidelines. Adults: The maximum daily dose is 20 mg per day. In order to reduce the risk of side effects the maintenance dose is achieved by upward titration 5 mg per week over the first 3 weeks as follows: Treatment should be started with 5 mg daily (half a tablet in the morning) during the 1st week. In the 2nd week 10 mg per day (half a tablet twice a day) and in the 3rd week 15 mg per day is recommended (one tablet in the morning and half a tablet in the afternoon). From the 4th week on, treatment can be continued with the recommended maintenance dose of 20 mg per day (one tablet twice a day). The tablets can be taken with or without food. Elderly: On the basis of the clinical studies the recommended dose for patients over the age of 65 years is 20 mg per day (10 mg twice a day) as described above. Children and adolescents under the age of 18 years: The safety and efficacy of memantine in children and adolescents have not been established. Renal impairment: In patients with normal to mildly impaired renal function (serum creatinine levels of up to 130 ?mol/l) no dose reduction is needed. In patients with moderate renal impairment (creatinine clearance 40 - 60 ml/min/1.73 m?) daily dose should be reduced to 10 mg per day. No data are available for patients with severely reduced kidney function (see sections 4.4 and 5.2). 3 Hepatic impairment: There are no data on the use of memantine in patients with hepatic impairment (see section 5.2). 4.3 Contraindications Hypersensitivity to the active substance or to any of the excipients. 4.4 Special warnings and special precautions for use As no data are available for patients with severe renal impairment (creatinine clearance less than 9 ml/min/1.73 m?) therapy is not recommended (see section 4.2). Caution is recommended in patients with epilepsy, former history of convulsions or patients with predisposing factors for epilepsy. Concomitant use of N-methyl-D-aspartate(NMDA)-antagonists such as amantadine, ketamine or dextromethorphan should be avoided. These compounds act at the same receptor system as memantine, and therefore adverse drug reactions (mainly CNS-related) may be more frequent or more pronounced (see also section 4.5). Some factors that may raise urine pH (see section 5.2 ?Elimination?) may necessitate careful monitoring of the patient. These factors include drastic changes in diet, e.g. from a carnivore to a vegetarian diet, or a massive ingestion of alkalising gastric buffers. Also, urine pH may be elevated by states of renal tubulary acidosis (RTA) or severe infections of the urinary tract with Proteus bacteria. In most clinical trials, patients with recent myocardial infarction, uncompensated congestive heart failure (NYHA III-IV), and uncontrolled hypertension were excluded. As a consequence, only limited data are available and patients with these conditions should be closely supervised. 4.5 Interaction with other medicinal products and other forms of interaction Due to the pharmacological effects and the mechanism of action of memantine the following interactions may occur: ? The mode of action suggests that the effects of L-dopa, dopaminergic agonists, and anticholinergics may be enhanced by concomitant treatment with NMDA-antagonists such as memantine. The effects of barbiturates and neuroleptics may be reduced. Concomitant administration of memantine with the antispasmodic agents, dantrolene or baclofen, can modify their effects and a dosage adjustment may be necessary. ? Concomitant use of memantine and amantadine should be avoided, owing to the risk of pharmacotoxic psychosis. Both compounds are chemically related NMDA-antagonists. The same may be true for ketamine and dextromethorphan (see also section 4.4). There is one published case report on a possible risk also for the combination of memantine and phenytoin. ? Other drugs such as cimetidine, ranitidine, procainamide, quinidine, quinine and nicotine that use the same renal cationic transport system as amantadine may also possibly interact with memantine leading to a potential risk of increased plasma levels. ? There may be a possibility of reduced serum level of hydrochlorothiazide (HCT) when memantine is co-administered with HCT or any combination with HCT. 4 Memantine did not inhibit CYP 1A2, 2A6, 2C9, 2D6, 2E1, 3A, flavin containing monooxygenase, epoxide hydrolase and sulphation in vitro. 4.6 Pregnancy and lactation Pregnancy: For memantine, no clinical data on exposed pregnancies are available. Animal studies indicate a potential for reducing intrauterine growth at exposure levels which are identical or slightly higher than at human exposure (see section 5.3). The potential risk for humans is unknown. Memantine should not be used during pregnancy unless clearly necessary. Lactation: It is not known whether memantine is excreted in humans breast milk but, taking into consideration the lipophilicity of the substance, this probably occurs. Women taking memantine should not breast-feed. 4.7 Effects on ability to drive and use machines Moderately severe to severe Alzheimer?s disease usually causes impairment of driving performance and compromises the ability to use machinery. Furthermore, memantine may change reactivity such that outpatients should be warned to take special care when driving a vehicle or operating machinery. 4.8 Undesirable effects In clinical trials in moderately severe to severe dementia, overall incidence rates for adverse events did not differ from placebo treatment and adverse events were usually mild to moderate in severity. The following table gives an overview of the most frequent (> 4% for memantine) adverse events (irrespective of causal relationship) that were observed in the trial population of patients with moderately severe to severe dementia. Preferred term (WHO ART) Memantine n=299 Placebo n=288 Agitation 27 (9.0%) 50 (17.4%) Inflicted Injury 20 (6.7%) 20 (6.9%) Urinary Incontinence 17 (5.7%) 21 (7.3%) Diarrhoea 16 (5.4%) 14 (4.9%) Insomnia 16 (5.4%) 14 (4.9%) Dizziness 15 (5.0%) 8 (2.8%) Headache 15 (5.0%) 9 (3.1%) Hallucination 15 (5.0%) 6 (2.1%) Fall 14 (4.7%) 14 (4.9%) Constipation 12 (4.0%) 13 (4.5%) Coughing 12 (4.0%) 17 (5.9%) 5 Common adverse reactions (1 - 10% and more frequent than with placebo) for memantine and placebo patients respectively were: hallucinations (2.0 vs. 0.7%), confusion (1.3 vs. 0.3%), dizziness (1.7 vs. 1.0%), headache (1.7 vs. 1.4%) and tiredness (1.0 vs. 0.3%). Uncommon adverse reactions (0.1 - 1% and more frequent than with placebo) were anxiety, hypertonia (increased muscle tone), vomiting, cystitis and increased libido. Based on spontaneous reports, seizures have been reported, mostly in patients with a history of convulsions. 4.9 Overdose In one case of suicidal overdosage the patient survived the oral intake of up to 400 mg memantine with effects on the central nervous system (e. g. restlessness, psychosis, visual hallucinations, proconvulsiveness, somnolence, stupor and unconsciousness) which resolved without permanent sequelae. Treatment of overdosage should be symptomatic. 5. PHARMACOLOGICAL PROPERTIES 5.1 Pharmacodynamic properties Pharmacotherapeutic group: Anti-dementia drugs, ATC code: N06DX01. There is increasing evidence that malfunctioning of glutamatergic neurotransmission, in particular at NMDA-receptors, contributes to both expression of symptoms and disease progression in neurodegenerative dementia. Memantine is a voltage-dependent, moderate-affinity uncompetitive NMDA-receptor antagonist. It blocks the effects of pathologically elevated tonic levels of glutamate that may lead to neuronal dysfunction. Clinical studies: A clinical trial in a population of patients suffering from moderately severe to severe Alzheimer's disease (MMSE total scores at baseline of 3 - 14) showed beneficial effects of memantine treatment in comparison to placebo over a treatment period of 6 months. In this multicenter, double-blind, randomised, placebo-controlled study, a total of 252 outpatients (33% male, 67% female, mean age 76 years) were included. The dosing was 10 mg memantine twice a day. Primary outcome parameters included assessment of the global domain (using the Clinicians Interview-Based Impression of Change (CIBIC-Plus)) and the functional domain (using the Activities of Daily Living Inventory (ADCS-ADLsev)). Cognition was assessed as a secondary endpoint with the Severe Impairment Battery (SIB). The results in these domains favoured memantine over placebo (Observed Cases Analysis for CIBIC-Plus: p=0.025; ADCS-ADLsev: p=0.003; SIB: p=0.002). After 6 months, the rate of individual responders (response prospectively defined as stabilisation or improvement in two independent domains) was 29% for the memantine group versus 10% for placebo (p=0.0004). With a triple criterion (response defined as stabilisation or improvement in all three domains: cognition, functional and global domain), there were 11% responders for memantine versus 6% for placebo (p=0.17). 6 5.2 Pharmacokinetic properties Absorption: Memantine has an absolute bioavailability of approximately 100%. tmax is between 3 and 8 hours. There is no indication that food influences the absorption of memantine. Linearity: Studies in volunteers have demonstrated linear pharmacokinetics in the dose range of 10 to 40 mg. Distribution: Daily doses of 20 mg lead to steady-state plasma concentrations of memantine ranging from 70 to 150 ng/ml (0.5 - 1 ?mol) with large interindividual variations. When daily doses of 5 to 30 mg were administered, a mean CSF/serum ratio of 0.52 was calculated. The volume of distribution is around 10 l/kg. About 45% of memantine is bound to plasmaproteins. Biotransformation: In man, about 80% of the circulating memantine-related material is present as the parent compound. Main human metabolites are N-3,5-dimethyl-gludantan, the isomeric mixture of 4- and 6-hydroxy-memantine, and 1-nitroso-3,5-dimethyl-adamantane. None of these metabolites exhibit NMDA-antagonistic activity. No cytochrome P 450 catalysed metabolism has been detected in vitro. In a study using orally administered 14C-memantine, a mean of 84% of the dose was recovered within 20 days, more than 99% being excreted renally. Elimination: Memantine is eliminated in a monoexponential manner with a terminal t? of 60 to 100 hours. In volunteers with normal kidney function, total clearance (Cltot) amounts to 170 ml/min/1.73 m? and part of total renal clearance is achieved by tubular secretion. Renal handling also involves tubular reabsorption, probably mediated by cation transport proteins. The renal elimination rate of memantine under alkaline urine conditions may be reduced by a factor of 7 to 9 (see section 4.4). Alkalisation of urine may result from drastic changes in diet, e.g. from a carnivore to a vegetarian diet, or from the massive ingestion of alkalising gastric buffers. Specific patient population: In elderly volunteers with normal and reduced renal function (creatinine clearance of 50 - 100 ml/min/1.73 m?), a significant correlation was observed between creatinine clearance and total renal clearance of memantine (see section 4.2). The effect of liver disease on the pharmacokinetics of memantine has not been studied. As memantine is metabolised to a minor extent only, and into metabolites with no NMDAantagonistic activity, clinically relevant changes in the pharmacokinetics are not expected in mild to moderate liver impairment. Pharmacokinetic/pharmacodynamic relationship: At a dose of memantine of 20 mg per day the cerebrospinal fluid (CSF) levels match the ki-value (ki = inhibition constant) of memantine, which is 0.5 ?mol in human frontal cortex. 5.3 Preclinical safety data In short term studies in rats memantine like other NMDA-antagonists have induced neuronal vacuolisation and necrosis (Olney lesions) only after doses leading to very high peak serum 7 concentrations. Ataxia and other preclinical signs have preceded the vacuolisation and necrosis. As the effects have neither been observed in long term studies in rodents nor in nonrodents, the clinical relevance of these findings is unknown. Ocular changes were inconsistently observed in repeat dose toxicity studies in rodents and dogs, but not in monkeys. Specific ophthalmoscopic examinations in clinical studies with memantine did not disclose any ocular changes. Phospholipidosis in pulmonary macrophages due to accumulation of memantine in lysosomes was observed in rodents. This effect is known from other drugs with cationic amphiphilic properties. There is a possible relationship between this accumulation and the vacuolisation observed in lungs. This effect was only observed at high doses in rodents. The clinical relevance of these findings is unknown. No genotoxicity has been observed following testing of memantine in standard assays. There was no evidence of any carcinogenicity in life long studies in mice and rats. Memantine was not teratogenic in rats and rabbits, even at maternally toxic doses, and no adverse effects of memantine were noted on fertility. In rats, foetal growth reduction was noted at exposure levels which are identical or slightly higher than at human exposure. 6. PHARMACEUTICAL PARTICULARS 6.1 List of excipients Tablet core: Lactose monohydrate Microcrystalline cellulose Colloidal anhydrous silica Talc Magnesium stearate Tablet coat: Methacrylic acid - ethyl acrylate copolymer (1:1) Sodium lauryl sulphate Polysorbate 80 Talc Triacetin Simethicone emulsion 6.2 Incompatibilities Not applicable. 6.3 Shelf life 4 years. 6.4 Special precautions for storage No special precautions for storage. 8 6.5 Nature and contents of container Blister packs containing either 7, 10, 14 or 20 tablets per blister strip (Alu/PP). Pack sizes of 28, 30, 50, 56, 100, 112 or 1000 (20 x 50) tablets are presented. Not all pack sizes may be marketed. 6.6 Instructions for use and handling No special requirements. 7. MARKETING AUTHORISATION HOLDER Merz Pharmaceuticals GmbH Eckenheimer Landstr. 100 D-60318 Frankfurt/Main Germany 8. MARKETING AUTHORISATION NUMBER(S) EU/1/02/218/001 EU/1/02/218/002 EU/1/02/218/003 EU/1/02/218/007 EU/1/02/218/008 EU/1/02/218/009 EU/1/02/218/010 9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 17/05/2002 10. DATE OF REVISION OF THE TEXT 9 SUMMARY OF PRODUCT CHARACTERISTICS 10 1. NAME OF THE MEDICINAL PRODUCT Axura 10 mg/g oral drops, solution. 2. QUALITATIVE AND QUANTITATIVE COMPOSITION 1 g of solution contains 10 mg of memantine hydrochloride (equivalent to 8.31 mg memantine). For excipients, see section 6.1. 3. PHARMACEUTICAL FORM Oral drops, solution. The solution is clear and colourless to light yellowish. 4. CLINICAL PARTICULARS 4.1 Therapeutic indications Treatment of patients with moderately severe to severe Alzheimer?s disease. 4.2 Posology and method of administration Treatment should be initiated and supervised by a physician experienced in the diagnosis and treatment of Alzheimer?s dementia. Therapy should only be started if a caregiver is available who will regularly monitor drug intake by the patient. Diagnosis should be made according to current guidelines. Adults: The maximum daily dose is 20 mg per day. In order to reduce the risk of side effects the maintenance dose is achieved by upward titration 5 mg per week over the first 3 weeks as follows: Treatment should be started with 5 mg daily (10 drops in the morning) during the 1st week. In the 2nd week 10 mg per day (10 drops twice a day) and in the 3rd week 15 mg per day is recommended (20 drops in the morning and 10 drops in the afternoon). From the 4th week on, treatment can be continued with the recommended maintenance dose of 20 mg per day (20 drops twice a day). The drops can be taken with or without food. Elderly: On the basis of the clinical studies the recommended dose for patients over the age of 65 years is 20 mg per day (10 mg twice a day) as described above. Children and adolescents under the age of 18 years: The safety and efficacy of memantine in children and adolescents have not been established. Renal impairment: In patients with normal to mildly impaired renal function (serum creatinine levels of up to 130 ?mol/l) no dose reduction is needed. In patients with moderate renal impairment (creatinine clearance 40 - 60 ml/min/1.73 m?) daily dose should be reduced to 10 mg per day. No data are available for patients with severely reduced kidney function (see sections 4.4 and 5.2). 11 Hepatic impairment: There are no data on the use of memantine in patients with hepatic impairment (see section 5.2). 4.3 Contraindications Hypersensitivity to the active substance or to any of the excipients. 4.4 Special warnings and special precautions for use As no data are available for patients with severe renal impairment (creatinine clearance less than 9 ml/min/1.73 m?) therapy is not recommended (see section 4.2). Caution is recommended in patients with epilepsy, former history of convulsions or patients with predisposing factors for epilepsy. Concomitant use of N-methyl-D-aspartate(NMDA)-antagonists such as amantadine, ketamine or dextromethorphan should be avoided. These compounds act at the same receptor system as memantine, and therefore adverse drug reactions (mainly CNS-related) may be more frequent or more pronounced (see also section 4.5). Some factors that may raise urine pH (see section 5.2 ?Elimination?) may necessitate careful monitoring of the patient. These factors include drastic changes in diet, e.g. from a carnivore to a vegetarian diet, or a massive ingestion of alkalising gastric buffers. Also, urine pH may be elevated by states of renal tubulary acidosis (RTA) or severe infections of the urinary tract with Proteus bacteria. In most clinical trials, patients with recent myocardial infarction, uncompensated congestive heart failure (NYHA III-IV), and uncontrolled hypertension were excluded. As a consequence, only limited data are available and patients with these conditions should be closely supervised. 4.5 Interaction with other medicinal products and other forms of interaction Due to the pharmacological effects and the mechanism of action of memantine the following interactions may occur: ? The mode of action suggests that the effects of L-dopa, dopaminergic agonists, and anticholinergics may be enhanced by concomitant treatment with NMDA-antagonists such as memantine. The effects of barbiturates and neuroleptics may be reduced. Concomitant administration of memantine with the antispasmodic agents, dantrolene or baclofen, can modify their effects and a dosage adjustment may be necessary. ? Concomitant use of memantine and amantadine should be avoided, owing to the risk of pharmacotoxic psychosis. Both compounds are chemically related NMDA-antagonists. The same may be true for ketamine and dextromethorphan (see also section 4.4). There is one published case report on a possible risk also for the combination of memantine and phenytoin. ? Other drugs such as cimetidine, ranitidine, procainamide, quinidine, quinine and nicotine that use the same renal cationic transport system as amantadine may also possibly interact with memantine leading to a potential risk of increased plasma levels. ? There may be a possibility of reduced serum level of hydrochlorothiazide (HCT) when memantine is co-administered with HCT or any combination with HCT. 12 Memantine did not inhibit CYP 1A2, 2A6, 2C9, 2D6, 2E1, 3A, flavin containing monooxygenase, epoxide hydrolase and sulphation in vitro. 4.6 Pregnancy and lactation Pregnancy: For memantine, no clinical data on exposed pregnancies are available. Animal studies indicate a potential for reducing intrauterine growth at exposure levels which are identical or slightly higher than at human exposure (see section 5.3). The potential risk for humans is unknown. Memantine should not be used during pregnancy unless clearly necessary. Lactation: It is not known whether memantine is excreted in humans breast milk but, taking into consideration the lipophilicity of the substance, this probably occurs. Women taking memantine should not breast-feed. 4.7 Effects on ability to drive and use machines Moderately severe to severe Alzheimer?s disease usually causes impairment of driving performance and compromises the ability to use machinery. Furthermore, memantine may change reactivity such that outpatients should be warned to take special care when driving a vehicle or operating machinery. 4.8 Undesirable effects In clinical trials in moderately severe to severe dementia, overall incidence rates for adverse events did not differ from placebo treatment and adverse events were usually mild to moderate in severity. The following table gives an overview of the most frequent (> 4% for memantine) adverse events (irrespective of causal relationship) that were observed in the trial population of patients with moderately severe to severe dementia. Preferred term (WHO ART) Memantine n=299 Placebo n=288 Agitation 27 (9.0%) 50 (17.4%) Inflicted Injury 20 (6.7%) 20 (6.9%) Urinary Incontinence 17 (5.7%) 21 (7.3%) Diarrhoea 16 (5.4%) 14 (4.9%) Insomnia 16 (5.4%) 14 (4.9%) Dizziness 15 (5.0%) 8 (2.8%) Headache 15 (5.0%) 9 (3.1%) Hallucination 15 (5.0%) 6 (2.1%) Fall 14 (4.7%) 14 (4.9%) Constipation 12 (4.0%) 13 (4.5%) Coughing 12 (4.0%) 17 (5.9%) 13 Common adverse reactions (1 - 10% and more frequent than with placebo) for memantine and placebo patients respectively were: hallucinations (2.0 vs. 0.7%), confusion (1.3 vs. 0.3%), dizziness (1.7 vs. 1.0%), headache (1.7 vs. 1.4%) and tiredness (1.0 vs. 0.3%). Uncommon adverse reactions (0.1 - 1% and more frequent than with placebo) were anxiety, hypertonia (increased muscle tone), vomiting, cystitis and increased libido. Based on spontaneous reports, seizures have been reported, mostly in patients with a history of convulsions. 4.9 Overdose In one case of suicidal overdosage the patient survived the oral intake of up to 400 mg memantine with effects on the central nervous system (e. g. restlessness, psychosis, visual hallucinations, proconvulsiveness, somnolence, stupor and unconsciousness) which resolved without permanent sequelae. Treatment of overdosage should be symptomatic. 5. PHARMACOLOGICAL PROPERTIES 5.1 Pharmacodynamic properties Pharmacotherapeutic group: Anti-dementia drugs, ATC code: N06DX01. There is increasing evidence that malfunctioning of glutamatergic neurotransmission, in particular at NMDA-receptors, contributes to both expression of symptoms and disease progression in neurodegenerative dementia. Memantine is a voltage-dependent, moderate-affinity uncompetitive NMDA-receptor antagonist. It blocks the effects of pathologically elevated tonic levels of glutamate that may lead to neuronal dysfunction. Clinical studies: A clinical trial in a population of patients suffering from moderately severe to severe Alzheimer's disease (MMSE total scores at baseline of 3 - 14) showed beneficial effects of memantine treatment in comparison to placebo over a treatment period of 6 months. In this multicenter, double-blind, randomised, placebo-controlled study, a total of 252 outpatients (33% male, 67% female, mean age 76 years) were included. The dosing was 10 mg memantine twice a day. Primary outcome parameters included assessment of the global domain (using the Clinicians Interview-Based Impression of Change (CIBIC-Plus)) and the functional domain (using the Activities of Daily Living Inventory (ADCS-ADLsev)). Cognition was assessed as a secondary endpoint with the Severe Impairment Battery (SIB). The results in these domains favoured memantine over placebo (Observed Cases Analysis for CIBIC-Plus: p=0.025; ADCS-ADLsev: p=0.003; SIB: p=0.002). After 6 months, the rate of individual responders (response prospectively defined as stabilisation or improvement in two independent domains) was 29% for the memantine group versus 10% for placebo (p=0.0004). With a triple criterion (response defined as stabilisation or improvement in all three domains: cognition, functional and global domain), there were 11% responders for memantine versus 6% for placebo (p=0.17). 14 5.2 Pharmacokinetic properties Absorption: Memantine has an absolute bioavailability of approximately 100%. tmax is between 3 and 8 hours. There is no indication that food influences the absorption of memantine. Linearity: Studies in volunteers have demonstrated linear pharmacokinetics in the dose range of 10 to 40 mg. Distribution: Daily doses of 20 mg lead to steady-state plasma concentrations of memantine ranging from 70 to 150 ng/ml (0.5 - 1 ?mol) with large interindividual variations. When daily doses of 5 to 30 mg were administered, a mean CSF/serum ratio of 0.52 was calculated. The volume of distribution is around 10 l/kg. About 45% of memantine is bound to plasmaproteins. Biotransformation: In man, about 80% of the circulating memantine-related material is present as the parent compound. Main human metabolites are N-3,5-dimethyl-gludantan, the isomeric mixture of 4- and 6-hydroxy-memantine, and 1-nitroso-3,5-dimethyl-adamantane. None of these metabolites exhibit NMDA-antagonistic activity. No cytochrome P 450 catalysed metabolism has been detected in vitro. In a study using orally administered 14C-memantine, a mean of 84% of the dose was recovered within 20 days, more than 99% being excreted renally. Elimination: Memantine is eliminated in a monoexponential manner with a terminal t? of 60 to 100 hours. In volunteers with normal kidney function, total clearance (Cltot) amounts to 170 ml/min/1.73 m? and part of total renal clearance is achieved by tubular secretion. Renal handling also involves tubular reabsorption, probably mediated by cation transport proteins. The renal elimination rate of memantine under alkaline urine conditions may be reduced by a factor of 7 to 9 (see section 4.4). Alkalisation of urine may result from drastic changes in diet, e.g. from a carnivore to a vegetarian diet, or from the massive ingestion of alkalising gastric buffers. Specific patient population: In elderly volunteers with normal and reduced renal function (creatinine clearance of 50 - 100 ml/min/1.73 m?), a significant correlation was observed between creatinine clearance and total renal clearance of memantine (see section 4.2). The effect of liver disease on the pharmacokinetics of memantine has not been studied. As memantine is metabolised to a minor extent only, and into metabolites with no NMDAantagonistic activity, clinically relevant changes in the pharmacokinetics are not expected in mild to moderate liver impairment. Pharmacokinetic/pharmacodynamic relationship: At a dose of memantine of 20 mg per day the cerebrospinal fluid (CSF) levels match the ki-value (ki = inhibition constant) of memantine, which is 0.5 ?mol in human frontal cortex. 5.3 Preclinical safety data In short term studies in rats memantine like other NMDA-antagonists have induced neuronal vacuolisation and necrosis (Olney lesions) only after doses leading to very high peak serum concentrations. Ataxia and other preclinical signs have preceded the vacuolisation and 15 necrosis. As the effects have neither been observed in long term studies in rodents nor in nonrodents, the clinical relevance of these findings is unknown. Ocular changes were inconsistently observed in repeat dose toxicity studies in rodents and dogs, but not in monkeys. Specific ophthalmoscopic examinations in clinical studies with memantine did not disclose any ocular changes. Phospholipidosis in pulmonary macrophages due to accumulation of memantine in lysosomes was observed in rodents. This effect is known from other drugs with cationic amphiphilic properties. There is a possible relationship between this accumulation and the vacuolisation observed in lungs. This effect was only observed at high doses in rodents. The clinical relevance of these findings is unknown. No genotoxicity has been observed following testing of memantine in standard assays. There was no evidence of any carcinogenicity in life long studies in mice and rats. Memantine was not teratogenic in rats and rabbits, even at maternally toxic doses, and no adverse effects of memantine were noted on fertility. In rats, foetal growth reduction was noted at exposure levels which are identical or slightly higher than at human exposure. 6. PHARMACEUTICAL PARTICULARS 6.1 List of excipients Potassium sorbate Sorbitol Purified water 6.2 Incompatibilities Not applicable. 6.3 Shelf life 4 years. Once opened, the contents of the bottle should be used within 3 months. 6.4 Special precautions for storage Do not store above 30?C. 6.5 Nature and contents of container Brown glass bottles (Hydrolytic Class III) with dropper containing either 20, 50, 100 g or 10 x 50 g solution. Not all pack sizes may be marketed. 6.6 Instructions for use and handling No special requirements. 16 7. MARKETING AUTHORISATION HOLDER Merz Pharmaceuticals GmbH Eckenheimer Landstr. 100 D-60318 Frankfurt/Main Germany 8. MARKETING AUTHORISATION NUMBER(S) EU/1/02/218/004 EU/1/02/218/005 EU/1/02/218/006 EU/1/02/218/011 9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 17/05/2002 10. DATE OF REVISION OF THE TEXT
-------------------- Omnicyclion.org higher knowledge starts here
Edited by Asante (08/21/04 06:37 PM)
|
Asante
Omnicyclion prophet
Registered: 02/06/02
Posts: 87,282
|
Re: Memantine -dissociative entheogenic pharm [Alzheimer's] *DELETED* [Re: Asante]
#3033562 - 08/21/04 05:32 PM (19 years, 7 months ago) |
|
|
Well.. as a contrasting profile here's the entire article on MEDLINE PLUS, an US gov't sponsored site that lays emphasis not on relatively benign psychotropic side effects but rather on the more physical side of things and barely mentions "hallucinations". Quote: -------------------------------------------------------------------------------- Drug Information: Memantine (Systemic) URL of this page: http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/500493.html Brand Names In the U.S.? Namenda Category Dementia symptoms treatment adjunct Description Memantine (me-MAN-teen ) is used to treat moderate to severe Alzheimer's disease. Memantine is not a cure for Alzheimer's disease but it can help people with the disease. Memantine will not cure Alzheimer's disease, and it will not stop the disease from getting worse. This medicine is available only with your doctor's prescription, in the following dosage forms: Oral Tablets (U.S.) Before Using This Medicine In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For memantine, the following should be considered: Allergies?Tell your doctor if you have ever had any unusual or allergic reaction to memantine. Also tell your doctor and pharmacist if you are allergic to any other substances, such as foods, preservatives, or dyes. Pregnancy?Memantine has not been studied in pregnant women. However, memantine has not been shown to cause birth defects or other problems in animal studies. Breast-feeding?It is not known whether memantine passes into breast milk. Although most medicines pass into breast milk in small amounts, many of them may be used safely when breast feeding. Mothers who are taking this medicine and who wish to breast feed should discuss it with their doctor. Children?Studies on this medicine have only been done in adult patients, and there is no specific information comparing the use of memantine in children with use in other age groups. This medicine is generally not used in children. Older adults?This medicine has been studied in older adults and has not been shown to cause different side effects or problems in older people than it does in younger adults. Other medical problems?The presence of other medical problems may affect the use of memantine. Make sure you tell your doctor if you have any other medical problems, especially: Kidney disease?patients with severe kidney disease should not use memantine, patients with mild or moderate kidney disease may need to take a smaller amount of memantine. Difficult urination Urinary tract problems Urinary tract blockage?memantine may make these conditions worse Epilepsy or history of seizures?memantine may make this medical condition worse Proper Use of This Medicine Dosing? The dose of memantine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of memantine. If your dose is different, do not change it unless your doctor tells you to do so. The number of tablets that you take depends on the strength of the medicine. Also, the number of doses you take each day and the time allowed between doses will be determined by your doctor. For oral For treatment of Alzheimer's disease Adults?To start, take 5 mg (milligrams) once a day. Your doctor may increase your dose gradually up to 10 mg (milligrams) twice a day. Children?This medicine is not used in children Missed dose? If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses. Storage? To store this medicine: Keep out of the reach of children. Do not store in the bathroom, near the kitchen sink, or in other damp places. Heat or moisture may cause the medicine to break down. Keep the medicine from freezing. Do not refrigerate. Do not keep outdated medicine or medicine no longer needed. Ask your health care professional how you should dispose of any medicine you do not use. Be sure that any discarded medicine is out of the reach of children. Precautions While Using This Medicine It is very important that your healthcare professional check your progress at regular visits to make sure that this medicine is working properly and to check for unwanted effects. Side Effects of This Medicine Side Effects of This Medicine Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention. Check with your doctor immediately if any of the following side effects occur: Less common Bloating or swelling of face, arms, hands, lower legs, or feet ; blurred vision; dizziness ; headache; nervousness ; pounding in the ears; rapid weight gain; slow or fast heartbeat; tingling of hands or feet; unusual weight gain or loss Other side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. However, check with your doctor if any of the following side effects continue or are bothersome. More Common Confusion Less common Anxiety; back pain; bladder pain; bloody or cloudy urine; change in walking and balance; chills ; clumsiness or unsteadiness; cough producing mucus; coughing; difficult, burning, or painful urination; difficulty breathing; difficulty moving; difficulty having a bowel movement (stool); diarrhea ; discouragement; dry mouth ; fear; feeling sad or empty ; fever; frequent urge to urinate; general feeling of discomfort or illness ; hyperventilation; insomnia ; irregular heartbeats; irritability; joint pain; loss of appetite; loss of bladder control; loss of interest or pleasure; lower back or side pain; muscle pain or stiffness; nausea; nervousness; pain; pain in joints; restlessness ; seeing, hearing, or feeling things that are not there; shortness of breath; sleepiness or unusual drowsiness; sore throat; tightness in chest; tiredness; trouble concentrating; trouble sleeping ; unusual tiredness or weakness; vomiting; wheezing P Other side effects not listed above may also occur in some patients. If you notice any other effects, check with your doctor. Developed: 03/02/2004 --------------------------------------------------------------------------------
-------------------- Omnicyclion.org higher knowledge starts here
Edited by Asante (08/21/04 06:26 PM)
|
Randolph_Carter
НơĻ?ĢΉōsŧ
Registered: 06/13/00
Posts: 29,281
Loc: Shroomery B-list.
Last seen: 13 years, 10 months
|
Re: Memantine -dissociative entheogenic pharm [Alzheimer's] *DELETED* [Re: Asante]
#3034178 - 08/21/04 08:01 PM (19 years, 7 months ago) |
|
|
Very interesting.... a dissociative that helps alzheimers....
points i was interested in: Agitation 27 (9.0%) 50 (17.4%)
Calming effect....definite dissociative....
and 4.9 Overdose In one case of suicidal overdosage the patient survived the oral intake of up to 400 mg memantine with effects on the central nervous system (e. g. restlessness, psychosis, visual hallucinations, proconvulsiveness, somnolence, stupor and unconsciousness) which resolved without permanent sequelae. Treatment of overdosage should be symptomatic.
At least a large does won't kill you, altho i'd really like an account of that individuals symptoms....but i'm always wishing for things i'll never get.
The half-life of this compound worries me from a recreational perspective.....i mean, if you have a long lived nmda antagonist in the system....and most users tend to not stick to one chemical... Altho, as previosly mentioned, i seriously doubt that this is going to be made anytime soon in a clandestine setting...most likely method of dispersment is diversion, like a few other chems we know of...
Still hunting down adamantine synth refs....
Hell of a breakthru if it works (and doesn't cause TOO sever hallucinations..... )
-------------------- "..all those molecules thrashing their kinky little tails, hot for destiny and the street." Gibson Nuke baby seals for Jesus! (This has been a +1 production.)
|
Viaggio
ChemicalConsumer
Registered: 07/05/03
Posts: 1,296
Last seen: 18 years, 6 days
|
Re: Memantine -dissociative entheogenic pharm [Alzheimer's] *DELETED* [Re: Asante]
#3034238 - 08/21/04 08:18 PM (19 years, 7 months ago) |
|
|
Because of a rare neurological condition, my doc is usually willing to write me a script for anything that has potential to improve my quality of life. The two features that raised my interest in Memantine was that it has neuroprotective traits (which may or may not apply to my disease), and that it might have effects similar to amphetamines?
My disease mainly involves the wasting of PNS tissue, which creates balance and cordination problems. When I use Adderall, there is some symptom improvement. Anyway, worth a shot?
-------------------- "...yet another in a long series of diversions an attempt to avoid responsibility."
|
Randolph_Carter
НơĻ?ĢΉōsŧ
Registered: 06/13/00
Posts: 29,281
Loc: Shroomery B-list.
Last seen: 13 years, 10 months
|
Re: Memantine -dissociative entheogenic pharm [Alzheimer's] *DELETED* [Re: Asante]
#3034512 - 08/21/04 10:06 PM (19 years, 7 months ago) |
|
|
more refs....as to specific action: http://www3.interscience.wiley.com/cgi-bin/abstract/9908/ABSTRACT
"In vitro studies with the non-radioactive analog, 1-amino-3-fluoromethyl-5-methyl-adamantane (19F-MEM) indicated that this compound binds selectively to the phencyclidine (PCP) binding site within the NMDA receptor complex"
Looks interesting, but i don't have a subscription.....mebbe thru a university access? www.blackwell-synergy.com/links/ doi/10.1111/j.0953-816X.2004.03297.x/enhancedabs/
http://www.pnas.org/cgi/content/full/97/23/12885 Discussion over the varying neuroprotective/neurodamaging effects of NMDA antagonists, based on type of neural degeneration...
This one kinda scares me....does this mean that the drug in question in this thread is slowly destroying the patients brain while bringing him slight symptom relief?
Heh....intermediate....http://www.chemicalland21.com/arokorhi/lifescience/phar/1,3-DIMETHYLADAMANTANE.htm
More adamantin addition refs.... http://www.kluweronline.com/article.asp?PIPS=493804&PDF=1
Alcohol dementia treatment? Memantine treatment in alcohol dementia: rapid PET changes and clinical course Preuss UW, Bahlmann M, Bartenstein P, Sch?tz CG, Soyka M Eur Neurol 2001; 45: 57-58
and that's the cream of the crop.
Any thoughts?
-------------------- "..all those molecules thrashing their kinky little tails, hot for destiny and the street." Gibson Nuke baby seals for Jesus! (This has been a +1 production.)
|
Hooty
Reality isRelative
Registered: 02/24/03
Posts: 2,467
Last seen: 12 years, 10 months
|
Re: Memantine -dissociative entheogenic pharm [Alzheimer's] [Re: Randolph_Carter]
#3035198 - 08/22/04 02:00 AM (19 years, 7 months ago) |
|
|
this is very interesting stuff.
-------------------- Without love in the dream It will never come true
|
Asante
Omnicyclion prophet
Registered: 02/06/02
Posts: 87,282
|
Re: Memantine -dissociative entheogenic pharm [Alzheimer's] *DELETED* [Re: Viaggio]
#3035960 - 08/22/04 10:48 AM (19 years, 7 months ago) |
|
|
Quote:
Because of a rare neurological condition, my doc is usually willing to write me a script for anything that has potential to improve my quality of life. The two features that raised my interest in Memantine was that it has neuroprotective traits (which may or may not apply to my disease), and that it might have effects similar to amphetamines?
My disease mainly involves the wasting of PNS tissue, which creates balance and cordination problems. When I use Adderall, there is some symptom improvement. Anyway, worth a shot?
I can only give one recommendation: Don't do it on your own. Personally I believe (believe = not hard fact) that the NMDA system is mostly based in the Central Nervous System, rather then the Peripheral one. (for n00bs: brain nerves/body nerves) Since its neuroprotective effect is basted on inhibiting damage through the N-Methyl-D-Aspartate pathway I think it might be of reduced or no value to you as our bud' Randolph Carter's find that it binds to the PCP receptor confirms it might well protect one system but by wrong use (or personal sensitivity) punch a hole in others.
The last thing somebody with PNS wasting needs is to have it driven by a CNS thats thrown off-balance by the wrong pharmaceutical.
On one way Memantine indeed has similarities to Amphetamine effects (perhaps some form of dopaminergic enhancement) but in another way it is a knock-down dissociative like PCP, Nitrous and Ketamine, only likely with a more benign profile.
It might help you or it might slow down a neural pathway that keeps vital systems (circulation, breath) up and my lack of knowledge about your condition creeps me out in the light of Memantine's slight tendency to epileptic seizures, a neural storm bad in most cases but maybe more likely to occur or more detrimental in your case.
What i think to be likely beneficial is sizable quantities of vitamine A, E and C, you might benefit from Ginkgo and perhaps Hydergine and Piracetam, but leave even the vitamin decisions to your doc.
In regard to yourself and the community at large I think the very best thing would be if you addressed a specific and direct email to the pharmboys of MERZ pharmaceuticals to inquire about how their new pharmaceutical might be of use in your specific case. They likely got -the- NMDA experts or they wouldnt market the first pharmaceutical of its kind.
It will likely provide you with the answers you need, but may also get them thinking along lines that may benefit humanity, considering the rarity of your condition it might not have been thoroughly reviewed in light of the therapeutic effect of Memantine (or its successors, no doubt they've got a dozen on ice that are almost ready) and its benefits and risks if they are convinced youmight even open up a new indication for Memantine's application, directly or indirectly.
If you like privacy, open a proxy email account from a public machine and work from there.
Be warned: the email box pharm co's leave often can only contain a light small text and won't be recieved by Shulgin, but rather somebody with a not-so-FAQ book.
Offer a correspondence emailbox and request an email address to pose a very specific question regarding specific usage in your case, which you'd best not be too clear about in the pilot mail to avoid a FAQ-intern parrotting "If its not on the list it is not advised" but rather lay your case on somebody higher up, preferably Research and Development where the whitecoats work their magic.
A pharm-corp consists of the marketing part (who think of lawsuits, company profile and annual sales) and the scientific part (who design the molecules, have access and insights into the reseach and in vitro/animal testing results, who in fact create the whole medicine and assign its indications and contra-indications. Without pissing anyone off make sure you've got somebody more to the sci side then a marketer. If you relay it through your doctor and let him add a personal accound of yours to his email its alot harder to dismiss.
A big plus is that it's a German multinational instead of an American Co. on its home turf, because we Europeans are more into knowledge-gathering for science sake while US companies have to legally worry a great deal for a $ 100.000.000 lawsuit if some dumbass swallows ten pills without pressing them out of the strip first
In the name of all thats sacred don't be casual about Memantine. If a pharm is close, close often means extra hazardous. It needs to be on the mark and only the experts can decide. If your doctor is too easy of prescribing he might not be the one to judge, but if his judgement has proven to be sound he might.
-------------------- Omnicyclion.org higher knowledge starts here
|
Asante
Omnicyclion prophet
Registered: 02/06/02
Posts: 87,282
|
Re: Memantine -dissociative entheogenic pharm [Alzheimer's] *DELETED* [Re: Randolph_Carter]
#3036168 - 08/22/04 12:00 PM (19 years, 7 months ago) |
|
|
Quote:
http://www3.interscience.wiley.com/cgi-bin/abstract/9908/ABSTRACT
"In vitro studies with the non-radioactive analog, 1-amino-3-fluoromethyl-5-methyl-adamantane (19F-MEM) indicated that this compound binds selectively to the phencyclidine (PCP) binding site within the NMDA receptor complex"
You bee naughty posting things like that
Quote:
Our findings have implications for clinical trials with NMDA antagonists, which were initiated in humans based on neuroprotection that has been demonstrated in rodent models of stroke and trauma on antecedent treatment. In patients undergoing cardiopulmonary bypass and subjected to antecedent treatment with the NMDA antagonist remacemide starting at 4 days before surgery, a beneficial effect on neuropsychomotor performance has been documented (30). These observations are in agreement with our findings showing that in rats subjected to antecedent treatment with CPP neuronal loss in the hippocampus after traumatic brain injury can be mitigated. It is also in agreement with the observation that MK801 and memantine prevent learning deficits in rats caused by acute damage of the hippocampus triggered by the NMDA agonist quinolinate (31).
In no other clinical trial, including those in stroke and head or spinal cord trauma, in which delayed treatment regimens with NMDA antagonists were chosen, could neuroprotective effects be confirmed so far (1) and in fact, in some trials, increased mortality prompted termination (32, 33).
In chronic neurodegenerative disorders, such as Huntington's or Parkinson's disease, symptomatological improvement with NMDA antagonists has been documented, but increases of survival or slowing of disease progression have not been reported so far (2). Symptomatological improvement seen in chronic neurodegenerative disorders with NMDA antagonists can be explained by their interaction with glutamate receptors in the basal ganglia that are involved in transmitting the symptoms of the disease to respective motor centers and not necessarily by prevention of degeneration of striatal or nigral neurons (34, 35).)
In light of our current findings, caution should be exercised when using NMDA antagonists as monotherapy in humans suffering from brain injuries or progressive neurodegenerative disorders with unknown mechanism of neuronal death. If our observations are valid for humans, our conclusions may explain why clinical trials have failed to identify neuroprotective effects of NMDA antagonists.
Alas.. so indeed it seems that in Alzheimer's the observed benefit may be derived from blocking the "offending stimuli", so it might in those cases offer temporary relief despite the steady, perhaps undiminished degradation, rather then slow or halt the disease.
Still in my view it is justified. Just because morphine does not cure a third degree burn nor remedy the actual neuronal stimuli its no excuse not to give it. Perhaps it -is- an alleviator in this case, more like Morphine is to pain then antivirals to AIDS. It would be very unfortunate, but it is proven to alleviate the subjective anguish of Alzheimers (and Huntington's) which is of great value. If a disease cannot be halted, combatting dysphoria is of highest importance, especially if it is associated with blocking deleterious action from reaching the motor centers.
In absence of a cure alleviating of the suffering is the next best thing.
Please note that it has been confirmed that in several kinds of neuronal damage it has damage-preventing or inhibiting effects if it is given prior to the injury which does mean the neuroprotection, in some cases, still stands.
What has to be determined is the nature of the neural degeneration, mas this will screen out the aiments that are worsened, and those of benefit before it even is administered.
Remember the dosages of 3-nitropropionic acid (nondrug poison agent) and the dissociatives might have been way off both interspecies and proportional to each other.
Did somebody get the Edgar Allen Poe feeling too when they described lifting rat-skulls, putting a metal plate to their little brains and inducing braindamage by hammering that plate with a drop-weight from a pre-determined distance just shy of squatting it? Anaesthesia was used and dissociatives followed in its wake, it will in the long run save millions of human lives (general research data is still good a century after the fact and has built that future) but damn people I just did my own animal experiment where i repeated the 38cm drop landing a 20gr brass weight on my head (i'm inquisitive ) and that rough simulation's quite an ouch even for a numbskull like me
Hmm.. any more contributors?
-------------------- Omnicyclion.org higher knowledge starts here
|
Psiloman
member
Registered: 04/11/03
Posts: 1,116
Loc: Europe
Last seen: 10 years, 6 months
|
Re: Memantine -dissociative entheogenic pharm [Alzheimer's] *DELETED* [Re: Asante]
#3037471 - 08/22/04 07:41 PM (19 years, 7 months ago) |
|
|
Well,i dont know if you could name that a contribution BUT...
I know of a proffesor in the university i used to work phor.Although i am in Genetics section and he works on neurobiology we have got a quite good relationship and we are talking about neurochemistry issues...I havent exactly come clean with him but we were talking lets say about 5HT-2a receptors agonism and he would get very exciting telling me that some agents (he didnt mention any names though ) have very interesting effects on perception and then all of a sudden he would stop talking as if he said too much...
well...TOday i talked to him again and i mentioned this drug,and his remark was "Does it have the psychoactive effects of...urrrmm..do you knwo ketamine?" and then he went all shy as if he "came out of the closet".I bet he is no stranger to psychedelics those "agonists of 5ht-2a" he mentioned i believed he reffered to classic entheogens.Anyhow,his father is suffering from alzheimers and he is afraid of it as well so he told me he will try to acquire some of this material to testi t.
I think he opened up to me and propably i will meet him tommorow to discuss the details of it ( i printed this thread so i can give him some info on it).I will also bring about the subject of entheogens.Wish me luck,maybe in some time i could document a bioassay (he look *personally* interested in its effects ,if you know what i mean )
|
Randolph_Carter
НơĻ?ĢΉōsŧ
Registered: 06/13/00
Posts: 29,281
Loc: Shroomery B-list.
Last seen: 13 years, 10 months
|
Re: Memantine -dissociative entheogenic pharm [Alzheimer's] *DELETED* [Re: Psiloman]
#3038234 - 08/22/04 11:57 PM (19 years, 7 months ago) |
|
|
As far as aquisition, one could look into the normal online pharmacy circles....sources say it's readily availible.
-------------------- "..all those molecules thrashing their kinky little tails, hot for destiny and the street." Gibson Nuke baby seals for Jesus! (This has been a +1 production.)
|
Asante
Omnicyclion prophet
Registered: 02/06/02
Posts: 87,282
|
Re: Memantine -dissociative entheogenic pharm [Alzheimer's] *DELETED* [Re: Psiloman]
#3038652 - 08/23/04 04:55 AM (19 years, 7 months ago) |
|
|
Quote:
FDA News FOR IMMEDIATE RELEASE P03-82 October 17, 2003 Media Inquiries: 301-827-6242 Consumer Inquiries: 888-INFO-FDA
FDA Approves Memantine (Namenda) for Alzheimer's Disease The Food and Drug Administration (FDA) today approved memantine (NAMENDA), for treatment of moderate to severe Alzheimer?s Disease. This is the first drug approved for the treatment of patients with this severity of disease. Previous treatments for Alzheimer?s Disease have been studied in less severely affected (mild to moderate) patients. Memantine?s mechanism of action is different from that of the drugs currently available for treating this disease.
Alzheimer?s Disease, which affects about 4.5 million Americans, is a degenerative condition affecting memory, judgment and the ability to reason. The new drug an -- N-methyl-D-asparate (NMDA) antagonist -- is thought to work by blocking the action of the chemical glutamate.
Although memantine helps treat the symptoms of Alzheimer?s Disease in some patients, there is no evidence that it modifies the underlying pathology of the disease.
FDA Commissioner Mark McClellan, M.D., Ph.D. said, "The approval of memantine is good news for Alzheimers? Disease patients. This is the first drug shown to have an effect on the symptoms of moderate to severe Alzheimer?s Disease, and shows a low incidence of minor side effects."
The first two double-blind studies, each of about six months duration, were conducted in the United States, and involved about 250 and about 400 patients, respectively. The larger study was carried out in patients already taking donepezil, a drug already approved for the treatment of Alzheimer?s Disease. Both studies showed that patients on memantine experienced less deterioration in their symptoms compared to patients treated with placebo during the study. The third study, conducted in nursing homes in Latvia, was a 12-week double blind study in 166 patients with severe Alzheimer?s Disease and also showed a statistically significant advantage of memantine over placebo.
The studies utilized a variety of measures to evaluate the effectiveness of memantine. For the two studies conducted in the United States, the measures included the Severe Impairment Battery (SIB) to assess attention, orientation, language, memory, and social interactions, and the modified Alzheimer?s Disease Cooperative Study ? Activities of Daily Living (ADCS-ADL) scale, which assessed the ability of patients to eat, dress, bathe, travel, shop and perform household chores.
The third study utilized the Behavioral Rating Scale for Geriatric patients (BGP), which assessed day-to-day functioning and the Clinical Global Impression of Change (CGI-C), which assessed the overall condition of the patients.
The most frequently reported adverse events were dizziness (seven percent), headache (six percent), and constipation (six percent).
FDA?s Peripheral and Central Nervous System Drugs Advisory Committee this past September unanimously agreed that memantine is effective and safe for the treatment of moderate to severe Alzheimer?s Disease. Memantine will be marketed under the trade name Namenda by Forest Labs of Jersey City, N.J.
Well the FDA stamps it basically the same as we found it in the literature: likely not a cure but possibly the very best thing around for alleviating the symptoms of even severe Alzheimer and perhaps more.
Please note how the abundant side-effects of "hallucinations" etc has been neutered out of the MERZ datasheet, showing only non-psychological side-effects in a desperate attempt to fog up the nature of NMDA-antagonists with drug warrior politics.
This is likely due to the gradual increasing of dosage and blending residual psychological effects in with the disorder for which it is given. If you gradually introduced LSD into somebody's system the paper would read: "slight increase in heartrate, pulse, respiration and mydriatic response to an unimportant degree" and they'd be right. Both "psychedelic" and "dissociative" effects can dwindle rapidly, perhaps more so in Alzheimer patients.
Psiloman: if the FDA makes this kind of statements it seems pretty well established safety and efficiency outweigh the risks in the large majority.
Since your professor works @ the neurology dept. he likely can get spectroscopically pure samples from MERZ for genuine research which whips the shit out of pharmaceutical quality when it comes to precise results. They likely got a couple of kilos on stock in R&D to begin with as its pretty cost-effective to let other institutions do bona fide research on your pharmaceutical pro deo
R&D is where the action is anyhoo because he can likely get information beyond medical usefulness from the lab boys which likely makes research unnecesary as MERZ will have made sure they know their shit
As for his father and the pharmaceutical side of things: many nations have an "experimental/orphan drugs regulation" which allows doctors to prescribe drugs that are not in the nation's current pharmacopeia but are present in others. It's typically applied to supply AIDS patients with novel medicines that are already approved in another nation, so local www AIDS groups and patient orgs will have the facts without having to consult a legal person. It would naturally require a doctor's approval and a signed paper that legally frees the doctor of responsiblities which may be hard depending on the degree of Alzheimer already present.
If his father still has lucid moments he should gather information as to life decisions which may be needed later on should he become incapable. Legally it is best for a tape recording to be made of this conversation.
Life is hash a times..
-------------------- Omnicyclion.org higher knowledge starts here
|
|