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Forcing Loperamide through the BBB

almost- said:
And I can tell you that >32mg doses with PGP inhibitors really work like an opiate.
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So taking 40mg Loperamide with a PGP inhibitor gives you some Opiate-like effect?

-What would be the effective dose of Garlic or Black Pepper to make Loperamide able to cause a central Opiate-like effect?

-If you need a large dose of Black Pepper or Garlic, how can you take it (I can't even imagine eating grams of Black Pepper... :( )

-Does anyone know what the potency of Loperamide can be, if used with a PGP inhitor?
(If we could completely inhibit PGP, taking 50mg Loperamide would be Codeine-like; weak; or much stronger an be more Hydrocone-like.

Sorry, I ask so many questions.... That's because there is very little info on the subject.
 
A few more questions (that subject, Loperamide, really haunts me...):

would a mix of Quinine + Quercetin + a PGP inhibitor (+ Cimetidine?) and a large dose (50mg) of Loperamide be dangerous?

=Would taking all the substances that help Loperamide getting thru the BBB ALL AT ONCE be dangerous?

(and would taking 3 substance making some of the Loperamide cross thru the BBB make 3x more Lopermaide cross the BBB?
(I think it's not as simple as that, that's why I ask...)

[Would the Quinine contained in a 1 liter Schweppes be enough to cause the effects described in some studies?
If it's the case, could I put some ground garlic in a Schweppes 1 liter bottle, let it sit for 1 day, filter, then dissolving some Quercetin in it; then drink the whole bottle, waiting 30 minutes, and then taking 50mg Loperamide be a good idea?
(would the infusion of Garlic in Shweppes have an unbarable taste?)]
 
jasoncrest said:
A few more questions (that subject, Loperamide, really haunts me...):

would a mix of Quinine + Quercetin + a PGP inhibitor (+ Cimetidine?) and a large dose (50mg) of Loperamide be dangerous?

=Would taking all the substances that help Loperamide getting thru the BBB ALL AT ONCE be dangerous?

(and would taking 3 substance making some of the Loperamide cross thru the BBB make 3x more Lopermaide cross the BBB?
(I think it's not as simple as that, that's why I ask...)

[Would the Quinine contained in a 1 liter Schweppes be enough to cause the effects described in some studies?
If it's the case, could I put some ground garlic in a Schweppes 1 liter bottle, let it sit for 1 day, filter, then dissolving some Quercetin in it; then drink the whole bottle, waiting 30 minutes, and then taking 50mg Loperamide be a good idea?
(would the infusion of Garlic in Shweppes have an unbarable taste?)]
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I think quinidine as opposed to quinine is required... I'm not sure if quinine could substitute for quinidine in this case. And yes, drinking a litre of ground up garlic in tonic water sounds absolutely disgusting. I'd be pretty surprised if you could actually drink the whole lot. Probably decarbonating it (ie letting it go flat) would help if you actually do decide to do it. To be honest I'd make a garlic infusion in 100mL or so of water and drink the tonic water and the infusion separately.
 
quinine as in schweppes doesnt work , i always had the idea it made my codeine highs with loperamide slightly better but thats probably just an idea.


you might try quinine sulfate tablets used for cleaning water you can get them in some pet shops for fish tanks and like.

and for the garlic i think they selll these tablets in health shops that might be an idea.


however to be honest i dont think youll ever get high of loperamide jcrest

its a nice potentiator (i get them for free usually ) but thats about it
 
BingeBoy said:
quinine as in schweppes doesnt work , i always had the idea it made my codeine highs with loperamide slightly better but thats probably just an idea.


you might try quinine sulfate tablets used for cleaning water you can get them in some pet shops for fish tanks and like.

and for the garlic i think they selll these tablets in health shops that might be an idea.


however to be honest i dont think youll ever get high of loperamide jcrest

its a nice potentiator (i get them for free usually ) but thats about it
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as someone mentioned previously, there is a guy who posts on alt.drugs.hard who has really recently been doing some experimenting with high doses of loperamide - 200mg or so. He swears that it gives him an opioid effect. Check out google groups with a search for: +purplepimp +loperamide or something
 
BingeBoy said:
quinine as in schweppes doesnt work
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Really? Why Not?

BingeBoy said:
however to be honest i dont think youll ever get high of loperamide jcrest
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Yes I know...
I don't really want to get high on it, I just want to know more about it, if it's possible, and how, etc... But it's only curiosity.
 
A little bit offtopic; I know quinine can cause blindness if overdosed. How much quinine is in Schweppes? Is there some warning labels in the bottles? "Do not drink over x bottles a day!" Would it be unhealthy to drink like 100 fl. oz. of Schweppes? Cheers.%)
 
jasoncrest said:
Really? Why Not?



Yes I know...
I don't really want to get high on it, I just want to know more about it, if it's possible, and how, etc... But it's only curiosity.
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there was a research paper on it posted n bluelight in which they used 1l of tonic before giving big doses of loperamide to study the effect (p-glycoprotein somehing something) .

but actually also because i tried it , in this sequence 1l of tonic and 20-40 mg of loperamide 1 hour later and then my codeine (usually 400 mg) 10 mins after that.

there was no difference with the same without the tonic.

i did think i noticed something at the first few times so i kept drinking the stuff but after a while i realized it was placebo or the ritual that made me feel slightly better (expectations etc).


as a poster already stated quinidine and not quinine is probably what might have a chance of succeeding in making loperamide cross the bbb more effectively.
 
Sneaky

Since this post is about me anyway i figure ill just skip the speculation, besides i dont really care what i post as TTD theres far worse i posted in the past still on the board, go look :)


So now, 10 grams? jesus christ, i dont think i used 10grams in a months time or longer.

Think about it now, they are 2mg pills, i was very very good at eating multiples of 10 of them at once without a problem, but GRAMS, jesus, 1 gram is 500 pills.

The point was that loperamide crosses the BBB anyway, but it cant get there if it gets metabolised first, which it does.

So you prevent it from being metabolised. I had that down to a science as well, down to the minute in fact. I got so i could tell if i was 5 minutes late taking the loperamide. It was all based on timetables, pill disolving rates, metabolism, digestive rate. Any drug that is metabolised by the same enzyme as loperamide will work as a potentiator. Quinine is a bad idea though.



I never would have done this at the doses i reached if i hadnt found bulk suppliers, i pushed my tollerance up a few times and raised the loperamide to match, which is why it was higher than 20mg.



Now, i can absolutely assure you with my life on the line, loperamide maintained my opiate dependance FULLY. And i dont mean after a few weeks off, i mean going straight from shooting oxycodone in huge amounts, to loperamiide. It kept it right on going.

Weather that has to do with Mu receptors, Kappa receptors, and where i have no idea. I can tell you they were central effects, not peripheral, it was absolutely CNS action, for a while it was even somewhat enjoyable, before i pushed the dose up really really high.

Its entirely possible the receptors that produced this effect werent even inside the BBB, i have no way of knowing, but it really doesnt matter though either does it?
 
So, while I'm chemistry stupid, this might be completely wrong.

On wikipedia:
Quinidine is a pharmaceutical agent that acts as a class I antiarrhythmic agent in the heart. It is a stereoisomer of quinine, originally derived from the bark of the cinchona tree.

Cinchona can be bought in the form of Chaser plus at a GNC or the like. "Cinchona 12X"

Could taking the chaser plus with the loperamide help to inhibit loperamide being metabolized? And getting some more of it to cross the BBB?

Also:

"Quinidine is the d- isomer of quinine. Quinidine is an
alkaloid that may be derived from various species of cinchona.
Cinchona barks contain 0.25 to 3.0% quinidine. Quinidine is
also prepared from quinine. Quinidine was first described in
1848 by Van Heymingen and it was prepared and given its
present name by Pasteur in 1853."

http://www.inchem.org/documents/pims/pharm/quinidin.htm#SectionTitle:1.5 Brand names, Trade names

And if its a step in the right direction, how much of the chaser plus would you have to take to prevent loperamide being metabolized?
 
The study used 600mg quinidine with 16mg of loperamide.

If the bark contains 3% quinidine and you have a 12X extract it would require about 1700mg (1.7g) of the extract to equal the 600mg quinidine.

12X * .03 * mg of extract required = 600mg

so mg of extract required = 600mg / (12X * .03)
mg of extract required = 1666.67mg ---> if 3%

mg of extract required = 600mg / (12X * .0025)
mg of extract required = 20000mg ---> if 0.25%

Of course these values probably mean little as there is no way to know the potency or quality of the extract. Adjusting the loperamide dose may also make a difference.

Also remember that this could be potentially dangerous.
 
^^^ I tried to google the 12X extract but it appears to only be sold in a combination Chaser product without a listing of how many mgs it contains! You obviously can't use this product. I want the 2 minutes that I spent doing algebra and typing these posts up back :)
 
I don't know whether to laugh or cry over the subject matter of this thread :\ 8)
 
5-HT2 said:
I don't know whether to laugh or cry over the subject matter of this thread :\ 8)
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Why?

"Discussion of journal articles, drug science and other theoretical topics"
 
just some FYI, i won't name the whole site but on *yn****i***.*** they seemed to have reached a conclusion... uh.. on something, with this whole loperamide shit...

I did a little research into loperamide today, specifically with regard to its pharmacokinetic properties, as an attempt to figure out what it is that's keeping it out of the brain. This problem is more complicated than just tweaking loperamide's functional groups to get it BBB-permeable. That is indeed one way to go about it, and loperamide's calculated polar surface area (PSA) is 43.8 square angstroms, which is definitely low for a CNS drug; I think 80-90 is a good range. I'm sure that tweaking polarity and bringing the PSA up would help loperamide get into the brain.

However, it turns out that loperamide is a P-glycoprotein (PGP) substrate, and undergoes active efflux transport away from the brain (ref in a second..). So even if you tweaked the molecule's polarity in favor of permeating the BBB, unless you lucked out and the change you made also wiped out its affinity for PGP, it will get grabbed and flung right back out by PGP. Blocking PGP transport of a drug intended for the CNS is tough and pretty much can't be done by clever interpretation of SAR tables. PGP has a broad range of substrates, and I'm not sure if all the ways in which it can bind substrates are yet fully understood. PGP can be thought of as a protective mechanism for the brain- its job is to keep foreign molecules from entering, and evolution has done a pretty good job with this one...

While reading I came across a paper that was specifically about the metabolism of loperamide, with emphasis on one type of metabolite in particular: N-alkyl-4-arylpyridinium type metabolites.

Drug Metabolism and Disposition, 32(9), pp. 943-952, (2004).
http://rapidshare.de/files/21824433/LoperamideMetabolism.pdf.html

One main topic of discussion in this paper is why loperamide isn't toxic. One of its metabolites is known to be a pyridinium-type species molecule, which is very similar to MPTP (N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), the neurotoxic metabolite of haldol that leads to the Parkinson's-like symptoms of tardive dyskinesia. That, and I once read something about clandestine chemists making shitty batches of demerol... but anyway, long story short, one hypothesis is that despite this metabolite being identified from loperamide, it's relatively safe and non-toxic specifically because it doesn't get into the brain, where the MPTP-like metabolite would do the real damage.

So with that in mind I'm not so sure loperamide is a good target for experimentation in this area. But please check the article out and see what you think..
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I dunno, haven't read the entire threads on both sites, but since they're separate (different forums), and i notice similar discussion going on, well, blah, if you know of the other forum go there and read that thread i guess, hehe..
 
I dunno what program he is using but on here:

http://www.daylight.com/meetings/emug00/Ertl/index.html

amphetamine gave a reading of 26 A2 and loperamide was about 45 A2.

I dont know what to make of this in light of the OP's comments about a high Molecular Polar Surface Area (PSA) being conducive to high CNS actvity. Fent has a PSA of 24 A2 for instance so wtf does this mean?

http://www.ncbi.nlm.nih.gov/entrez/...ve&db=PubMed&list_uids=10554091&dopt=Abstract

Maybe LOWERING the PSA is in order?

Ya removing the chlorine and OH lowers it to 24. Making the ester didnt really help with this 8(

Ketobemidone gives a value of 40.54 A2 though 8(

My gut feeling is loperamide is just a sewer bate drug, one doesnt need to understand the "science" to understand that this drug is crappy.
 
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hehehe

This is amusing, everyone speaking from the idea of getting high with it, hahaha

I posted because it was useful for MAINTENANCE. Lots of people have spoken to me about it as well for that reason.

You can theorize all you want, but it worked and i dont care how, i never did care.

BTW, taking loperamide by itself is probably more dangerous than with something to inhibit its metabolism, perhaps not in the brain but elseware.

It seems that every time i took cimetidine before it, i had no problems, whereas everytime ive ever taken loperamide alone, even in small amounts, its absolutely not fun and damn near uncomfortable.

I also took note of the metabolites in the study, that were related to MPTP and MPPP if i got the names right, those were metabolites of a synthetic demerol analog in the 80s, that caused all sorts of symptoms. Even if loperamide did metabolise into a toxic agent, and it did have some effect, i have yet to notice, though i make no claims either way :)

I never noticed any problems, perhaps ill be wrong about that by the time im 70 :)
 
MPPP was the desired analog, and MPTP was the accidental analog produced by heating the solution too quickly at too high of a temperature
 
I will be the guinea pig here. I just took 1500mg of quercetin and I have 100 mg of loperamide. How much loperamide should i take and how long after i took the quercetin should i wait to take the loperamide.
 
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