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OfflineMorphogenesis
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NBOMe compounds and "complexed blotters"
    #15525887 - 12/16/11 11:59 AM (12 years, 2 months ago)

What's the good word on the NBOMes? I've read a few reports on 25i.

I just learned that complexing the blotters with 2-Hydroxypropyl-Beta-Cyclodextrindsad supposedly enhances bio-availability or absorption somehow?


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Invisibleabltsandwich
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Re: NBOMe compounds and "complexed blotters" [Re: Morphogenesis]
    #15526063 - 12/16/11 12:46 PM (12 years, 2 months ago)

So what you spray your 25i-nbome with Febreze and you get better results?  First I've heard of it. :shrug:


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OfflineMorphogenesis
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Re: NBOMe compounds and "complexed blotters" [Re: abltsandwich]
    #15526086 - 12/16/11 12:51 PM (12 years, 2 months ago)

"Complexed with a ratio of HPBCD" - this information appears in many different places.

What did you think of 25i?


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Re: NBOMe compounds and "complexed blotters" [Re: Morphogenesis]
    #15526104 - 12/16/11 12:55 PM (12 years, 2 months ago)

I've not tried it yet, color me very interested though.


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OfflineMorphogenesis
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Re: NBOMe compounds and "complexed blotters" [Re: abltsandwich]
    #15528906 - 12/17/11 12:55 AM (12 years, 2 months ago)

Found the answer here on the Shroomery:

"2-hydroxypropyl-ß-cyclodextrin (HPßCD). Basically the NBOMe and HPßCD is dissolved in EtOH (I've read that the best ratio is around 1NBOMe 1:8 HPBCD) and then used for laying blotter or for more effective liquid dosing. The amount of ethanol used will depend on the type of blotter. It still needs to be taken via sublingual, buccal or nasal administration, it just makes it more effective."


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Offlinemellowparty
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Re: NBOMe compounds and "complexed blotters" [Re: Morphogenesis]
    #15529242 - 12/17/11 04:08 AM (12 years, 2 months ago)

I think HPBCD assumes this toroidal conformation with its more hydrophobic parts to the inside and hydrophilic to the outside. Look at this structure and see for yourself:



And then your hydrophobic molecule in this case 25i gets trapped inside the hydrophobic bit (cause its hydrophobic itself) and effectively the HPBCD serves as a vehicle to account for the 25i's poor solubility. Imagine you want to get from point A to point B and there is a sea in between. You get on a boat and cross easily, otherwise you hate water and are just stuck at point A. You're the 25i and the boat is HPBCD.



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OfflineMorphogenesis
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Re: NBOMe compounds and "complexed blotters" [Re: mellowparty]
    #15529493 - 12/17/11 07:29 AM (12 years, 2 months ago)

I understand the general hydrophobic effect of certain molecules ('amphiphiles' display both polar & non-polar affinity), but I'm still unsure as to how the HPßCD over-rides this property in 25i in order to enhance bioavailability. Transmucosal absorption is the ROI for blotter, so how does HPßCD make my tongue and cheeks more receptive - or the molecule more compatible, to be more exact?


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Offlinemellowparty
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Re: NBOMe compounds and "complexed blotters" [Re: Morphogenesis]
    #15529603 - 12/17/11 08:24 AM (12 years, 2 months ago)

Well if 25i is not very soluble how would you expect it to cross the mucosa and enter your bloodstream?


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Offlinemellowparty
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Re: NBOMe compounds and "complexed blotters" [Re: mellowparty]
    #15529604 - 12/17/11 08:25 AM (12 years, 2 months ago)

Or you are referring to something more specific rather than simply a matter of being soluble/insoluble?


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OfflineMorphogenesis
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Re: NBOMe compounds and "complexed blotters" [Re: mellowparty]
    #15529611 - 12/17/11 08:27 AM (12 years, 2 months ago)

Quote:

mellowparty said:
Or you are referring to something more specific rather than simply a matter of being soluble/insoluble?




I understand conceptual solubility, looking for molecular explanation.


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Offlinemellowparty
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Re: NBOMe compounds and "complexed blotters" [Re: Morphogenesis]
    #15529652 - 12/17/11 08:38 AM (12 years, 2 months ago)

Since 25i has bulky hydrophobic bits then the water molecules would form ordered clathrate structures around it. This would reduce the entropy of the solvent thus making the whole process thermodynamically unfavourable. So in essence there would be the propensity to increase the entropy of the solvent and lose the ordered clathrate cages which should clump the hydrophobic molecules together reducing their availability for the organisms. So since all systems try to reach maximum entropy when you add HPBCD the clathrates would be exchanged for the hydrophobic core of the HPBCD toroid and therefore increase the entropy of the solvent. This along with equilibrium (drug+HPBCD-->complex) would be the thermodynamic drivers to increase the water solubility of the drug thus making it easy for the drug to undergo transepithelial absorption. And then as the drug binds to the 5-hydroxytryptamine receptors free energy would be released further driving the import of the drug into the blood stream, through the BBB and straight to the receptor binding site.


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OfflineMorphogenesis
Theatre Semiotics

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Re: NBOMe compounds and "complexed blotters" [Re: mellowparty]
    #15529680 - 12/17/11 08:46 AM (12 years, 2 months ago)

Thanks, going to read/research now based on those details.


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Offlinemellowparty
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Re: NBOMe compounds and "complexed blotters" [Re: Morphogenesis]
    #15529695 - 12/17/11 08:52 AM (12 years, 2 months ago)

So that the physics behind and its all good. What I don't know is how exactly the complex traverses the epithelia lining the GIT. Would there be lectin based receptors that bind the sugary backbone of HPBCD to trigger conformational changes in their cytoplasmic domains to promote adaptor protein and clathrin dependent/indipentent assembly of endocytic vesicles etc. Post the results of your research when you're done :yesnod:


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OfflineMorphogenesis
Theatre Semiotics

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Re: NBOMe compounds and "complexed blotters" [Re: mellowparty]
    #15533462 - 12/18/11 02:34 AM (12 years, 2 months ago)

More explanations:

HPBCD likely causes 95% sublingual absorption of hydrophobic drugs in 20 minutes (Pitha, Joseph, study on HPBCD complexed testosterone).

More here: http://www.drugs-forum.com/forum/showthread.php?t=96980#ixzz1gsRS9AxI

From the thread:

How HPBCD (hydroxy-propyl-beta-cyclodextrin) works to significantly improve buccal/sublingual
absorption:

http://www.pharmainfo.net/reviews/cy...systems-update

http://www.aapspharmscitech.org/view.asp?art=pt060243

Poster says, 'think of it as like a "molecular condom" that fits the drug so that it can be delivered across sublingual/buccal membranes with significantly improved efficiency.'


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