Loperamide: The pseudo of opioids?

A while back SWIM had another handle on another forum, and we got to discussing loperamide(Immodium). it is an opioid that doesn't cross the blood brain barrier. however, it shares a lot of its structure w/ demerol/fentanyl opioids, and maybe turning that hydroxyl onto a methoxy or just reducing it will help this little drug realize its full potential. id tell you to refer to the opiod chemistry forum on Drugs-Forum, but those information-fascists want you to write a fucking term paper just to get into the advanced chem forums. any ideas?? Below is loperamide, and next i'll post a fentanyl structure so yous can see the similarities.

 

and this is fentanyl. maybe the problem w/ loperamide is both hydroxy and chloro group on aromatic ring

 

Interesting theory.

 

Will be a major chemical undertaking to reduce the hydroxyl group and that chloro group, if it wasn't then underground chemists would be making fentanyl out of loperamide like crazy!!

 

actually someone hinted on the old forum thread that it may be possible with a reduction similar to reducing pseudo

 

and some info i found says loperamide actually has demerol and methadone-like properties. cant be any harder than making o-desmethyltramadol, the opioid RC

 

Any legit vendors for o-desmethyltramadol ?

 

im out of that loop. in 08 I had a good site that even sent me a sample of 2ct21 at the jump off, but im dying for a hookup now. ill order anything.
but i know that most of the sites that have phenazepam also have o-desmethyltramadol. and I'd be willing to bet there will be an active loperamide analog availalble soon. or even diphenoxylate, another quasi-opioid.
you're better off trying to find 7-hydroxymitragynine, the metabolite of Kratom. supposedly a good opioid though i never had it. some of those ethnobotanical possibly.

 

:bobby:

 

[FONT=&quot]The amide carbonyl group of DiPOA is a mimic of the hydroxyl group of loperamide and the ester group of carfentanil, which may participate in hydrogen bond interactions with the mu receptor [/FONT][FONT=&quot][/FONT]
[FONT=&quot]BBB[/FONT][FONT=&quot] transport of a parent drug can be hindered by the addition of a [/FONT][FONT=&quot]hydroxyl[/FONT][FONT=&quot] group, which can result in an agent that is relatively more [/FONT][FONT=&quot]polar[/FONT][FONT=&quot] and less likely to penetrate the barrier.[/FONT][FONT=&quot][/FONT]
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[FONT=&quot]SN2 substitution, in which the iodide ion replaces the "activated" hydroxyl group of loperamide would allow it to cross the blood brain barrier.[/FONT]
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[FONT=&quot]Quinine like quinidine is a p-glycoprotein however only quinidine with loperamide was found to produce respiratory depression, indicative of central opioid action. Quinine is combined with acetic acid and potassium iodide to yield quinidine hydriodide. The potash of iodide used to seperate quinidine from quinine replaces the "activated" hydroxyl group (water) with an iodide ion. The hydriodide of quinidine replaces both the hydroxyl group of loperamide and it inhibits p-glycoprotein.This duel action is why only quinidine with loperamide via the SN2 substitution was found to produce respiratory depression, indicative of central opioid action.[/FONT]
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[FONT=&quot]Many people don't realize that inhibiting p-glycoprotein alone without trying to remove the polar hydroxyl group of loperamide is why only the hydriodide of quinidine was found to produce respiratory depression, indicative of central opioid action. The hydroxyl group of loperamide is polarand this factor makes it less likely for loperamide to penetrate the blood brain barrier and enter into the CNS. [/FONT]
[FONT=&quot]Cometta-Morini et al., 1992).[/FONT] [FONT=&quot]Loperamide initially cross the blood barrier and then is immediately pumped back out into the non–central nervous system (CNS) circulation by P-glycoprotein. The p-glycoprotein and hydroxyl group of loperamide keeps loperamide a peripherally restricted mu opioid agonist.[/FONT]

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[FONT=&quot]Some novel agents that inhibit p-glycoprotein include limonin which is isolated from [/FONT][FONT=&quot]from the seeds of valencia oranges and lemons. Piperine (a constituent of black pepper) is both an inhibitor of p-glycoprotein and an inhibitor of CYP3a4. Piperine is extracted from black pepper using dichloromethane.[/FONT][FONT=&quot] Omeprazole is useless as a p-glycoprotein inhibitor since it has a very short half-life.[/FONT]

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