PDA

View Full Version : Forcing Loperamide through the BBB



Pages : [1] 2

jasoncrest
23-05-2006, 19:09
There's a thread by TheTripDoctor on Loperamide in Other Drugs, it seems that he found the way to enjoy Loperamide....

In the thread, it has been said that the way to feel an effect from Loperamide is to take a very large amount of it (just like GABA doesn't cross the BBB, but is taken in 1 to 5 grams doses, so a part of it goes through the BBB)

I would like to read an advanced drug discussion on this subject.

#Is it true that if you take a very large amount of a substance that doesn't cross the BBB, some of it will cross the BBB.

#If this is true, is it possible to know how many mgs Loperamide will cross the BBB if you eat 10 grams of Loperamide?

(If there's no answer to this question, do we know how many mgs GABA cross the BBB when someone eat 10 grams of GABA powder?)

Any input, info?

robatussin
23-05-2006, 21:54
would the consipation rate be worth it? 10 grams is at least 5000 times the recommended dose

Smyth
23-05-2006, 22:38
Steve actually said 50mg did the job but that u have to take some other weird antihistamine pill to potentiate the loperamide. But u cant just go into a pharmacy store or u end up paying too much money since loperamide is not distributed in units that can maintain this dose.

raybeez
23-05-2006, 22:56
Steve actually said 50mg did the job but that u have to take some other weird antihistamine pill to potentiate the loperamide. But u cant just go into a pharmacy store or u end up paying too much money since loperamide is not distributed in units that can maintain this dose.


^^^

My understanding of his post was that loperamide was active if:

1. Large doses were taken (ie 50mg)
2. Smaller doses were taken with tagamet, which increased the bioavailability/AUC of the drug by inhibiting its metabolism.

mitogen
24-05-2006, 00:31
would the consipation rate be worth it? 10 grams is at least 5000 times the recommended dose

good fucking point. there is no god damn WAY that I would want to take an overdose of this stuff. I already have bad enough constipation and haemarrioids as it is. I wonder what would actually happen to your GI tract if you took that much. Seems we have a guinea pig... Perhaps we could ask him to give an experience report...;)

We were actually talking about this a while ago if you look in the archives. Maybe 6 months ago? I think it turned out that loperamide does actually cross but is pumped out straight away by P-glycoprotein. Better check that... We decided that a combination of the correct CYP450 inhibitor and a P-glycoprotein inhibitor should allow the loperamide to stay in the brain long enough to have an effect. We discussed various PGP inhibitors and basically came to the conclusion that yes this was feasible, but a.) PGP is there to protect the brain, and is probably something that is not really worth screwing around with, and b.) PGP inhibitors are not that common/accessible, and are usually lab-grade [2 problems with this are accessibility, and the fact that only very small amounts would be used in labs to treat cell cultures etc. so one probably wouldn't be able to obtain enough from a lab to actually dose with]

jasoncrest
24-05-2006, 13:52
I was just curious. (very curious in fact).

I wouldn't take large doses of Loperamide, it would be too expansive, and I think the side-effects aren't worth it...
(and I'm on Methadone by the way, and can get Morphine for a cheap price)

But I'm still curious....
What doses of Loperamide would be equivalent to 300mg Codeine?

(or: when a substance is unable to cross the BBB, how many do you have to take to make some of it cross the BBB?)

BingeBoy
24-05-2006, 14:03
^
yeah i always use it for potentiation cause its the cheapest thing around in holland however in france its fricking expensive (1 euro here)

i took like 40 mg doses with say codeine and it really helps it along

however in those kind of doses it can be very bad for you and damage the intestines i found out the bad way although i never had a doctor check it out.


and it doesnt work that way jcrest , maybe 30 mg of loperamide equals 20-40 mg of codeine in the head but like 400-500 in the body without the histamine release.

however its very good for potentiating when taken a bit before the other opiate the loperamide will fill up the opiate receptors in your body so more of the good opiate will go to your brain.

however i think with your prices it aint wort it

i like it because is potentiation without interference like with a benzo or an antihistamine

splenda
24-05-2006, 14:07
I was just curious. (very curious in fact).

I wouldn't take large doses of Loperamide, it would be too expansive, and I think the side-effects aren't worth it...
(and I'm on Methadone by the way, and can get Morphine for a cheap price)

But I'm still curious....
What doses of Loperamide would be equivalent to 300mg Codeine?

(or: when a substance is unable to cross the BBB, how many do you have to take to make some of it cross the BBB?)
That really is unchartered ground, what you're asking.

We don't have conclusive evidence yet as to the (exact) amount of loperamide it takes to cross the BBB, or if everything is just a very good placebo effect.

8( 8(

BingeBoy
24-05-2006, 14:16
^
its not placebo

loperamide should not be used on people under 12 years old

and drowsiness is listed as a side effect on the generic loperamide leaflet over here (netherlands)

its terribly horribly weak since it hardly crosses the blood barrier

Abraxus
24-05-2006, 15:05
I just read a post today in the alt.drugs.hard newsgroup by a poster named Purple Pimp 2121. He claims to have ingested 200mg of loperamide and that he got high from it. There have been a few posts there about it from this poster, and he seems quite convinced that taking high doses produces a definate opiate effect. I haven't tried it, and probably won't. Definately a less than scientific experiment, but it's something. He also states that the constipation from such a dose is not as bad as with a high dose of any other opiate and that an OTC laxative cures it.

jasoncrest
24-05-2006, 19:33
If there's an Opioid related to Fentanyl, OTC in almost every country, that can give opiate-like effects at the 200mg dose (which is not a dose for an Opioid, you need more than 200mg of many opiate like Morphine, Meperidine/Pethidine, Codeine, Meptazinol to feel a strong effect orally), this should be tried by someone...

I really would like to try it (even if 200mg Loperamide would be more expansive than 14 tablets of 100mg Morphine capsules), if I was not on Methadone.

It seems to be foolish or dumb, but this is only because Loperamide has been commercialized in 2mg doses for decades...
If Loperamide was commercialized as 800mg capsules for strong chronic pain, the idea of getting high on it wouldn't be so surprising...

(it would have MANY side-effects, there would be a big overdose risk, but this is already the case with many Opioids commercialized, isn't it?)

BingeBoy
24-05-2006, 19:51
related to fent but if it crossed the blood barrier like fent 2 mg would kill most people now wouldnt it.

i could try it but i already know it would be crap an opiate virgin might get a nod going on from as little or much as 100.

also you should look into snorting it , i think it would definetly help with getting it to your brain (this isnt very scientific but eck if someone is gonna do some experimenting)

if you guys raise the funds ill go find an willing opiate virgin

Abraxus
24-05-2006, 19:55
related to fent but if it crossed the blood barrier like fent 2 mg would kill most people now wouldnt it.

i could try it but i already know it would be crap an opiate virgin might get a nod going on from as little or much as 100.

also you should look into snorting it , i think it would definetly help with getting it to your brain (this isnt very scientific but eck if someone is gonna do some experimenting)

if you guys raise the funds ill go find an willing opiate virgin

Excellent...We shall sacrifice said opiate virgin at midnight June 6, 2006. The opiate gods will be pleased, no?

BingeBoy
24-05-2006, 19:56
yes lets hope he goes blue in the name of junky science

DrEIMiller
24-05-2006, 22:53
I wzas searching thtrough google groups today as well and there was talk of using quercetin (a flavnoid) to get more loperimide to cross the BBB. And there was study done at Temple where quinidine was used to increase the amount of loperimide crossing the BBB.

The quercetin is OTC at health food stores. This was purely hypothetical, I think someone said it could possible work but no amounts and methods of admin were specified.

The quinidine (a sterepisome of quinine) had definite opiate response - pupil constriction, etc. I believe it was 600 mg of quinidine and 16 mg of loperamide.

I see if I can find the info and repost it here.

DrEIMiller
24-05-2006, 23:00
This post references both quercetin and quinidine

Steve Dyer wrote (several months ago):


> It turns out, however, that this behavior of loperamide is
> the result of the activity of a specialized ATP-activated "G protein"
> whose job it is to pump out such nasty stuff back across the blood
brain
> barrier as fast as it arrives. If you overwhelm the G protein by
keeping
> it busy with something else, loperamide once again becomes a
traditional
> mu opioid drug. Mice that lack this G protein which have been
administred
> loperamide behave like they've been given overdoses of morphine and
then
> they die. The only allusion I've seen to human beings has been a
recent
> abstract which reported that people taking 16mg of loperamide (8 2mg
caps)
> along with 600mg quinidine (a stereoisomer of quinine used as an
> antiarrythmic drug) exhibited uncharacteristic "respiratory
depression"; no
> comments on the degree of respiratory depression (a characteristic of
> mu-opiate activity), nor how it make them feel.

> I'm no expert on this subject, but there are probably whole families
of
> specialized G proteins which act as "pumps" against certain toxins
> (such mechanisms have been implicated in the development of resistance
> to certain toxic cancer chemotherapeutic agents such as cisplatin.)
> At the very least, this would suggest some caution using loperamide in
> people taking quinidine. 600mg of quinidine is hardly a harmless drug
> itself to produce an unquantified and itself potentially dangerous
high
> from an otherwise licit OTC product. But it makes you wonder what
else
> would be a suitable substrate for this G protein.



If there's any substrate suitable for turning loperamide
(e.g. Imodium brand) into a drug of abuse, I think
I know what it is.

There are several membrane proteins (MDR1, MRP1-6)
which have been identified (or tenatively identified) as
drug efflux pumps responsible for multidrug resistance
in cancer chemotherapy. They have in common the
ATPase binding cassette (ABC) [1].


Quercetin, a flavonoid, is known to inhibit these pumps
by inhibiting the ATPase activity [2, 3]. Quercetin is
easily absorbed in large quantity from the gut [4] and
well-tolerated by the IV route [5]. Quercetin is widely
available in oral dosage forms from so-called "health
food" stores, and in pure form over the Internet.


Therefore, I predict loperamide with quercetin is the
magic combination which would have opioid activity
in the central nervous system.


1. Kool et al, "MRP3, an organic anion transporter
able to transport anti-cancer drugs", PROC NAT
ACAD SCI, v 96, p 6914-6919.


2. Conseil et al, "Flavonoids: A class of modulators
with bifunctional interactions at vicinal ATP- and
steroid-binding sites on mouse P-glycoprotein",
PROC NAT ACAD SCI, v 95, p 9831-9836.


3. Shapiro and Ling, "Effect of Quercetin on
Hoechst 33342 Transport by Purified and
Reconstituted P-Glycoprotein, BIOCHEM
PHARMACOL, v 53, p 587-596.


4. Wiseman, "The bioavailability of non-nutrient
plant factors: dietary flavonoids and phyto-
oestrogens", PROC NUTR SOC, v 58,
p 139-146.


5. Ferry et al, "Phase I Clinical Trial of the
Flavonoid Quercetin: Pharmacokinetics and
Evidence for _in_Vivo_ Tyrosine Kinase
Inhibition", CLIN CANCER RES, v 2,
p 659-668.


http://groups.google.com/group/sci.med.pharmacy/browse_thread/thread/e8d603f255af18fa/546746858d2fc5bd?q=loperamide+quinidine&rnum=1#546746858d2fc5bd

BilZ0r
25-05-2006, 01:43
^ Steve Dyer is a bit confused. It's not a G-protein, they are multidrug transporters, like P-glycoprotein.

Unfortunately, I don't really think I believe that there was a study where animals died from loperamide mediated opioid overdose after inhibition of multidrug transporters as cited above. Inhibition of these transporters in animals by knockout of the gene, or with quinidine, causes about a 10x increase in uptake of the drug [1 (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14698039&query_hl=1&itool=pubmed_docsum)]. Still, in humans quinidine has some effects on loperamide [2 (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14583678&query_hl=6&itool=pubmed_docsum)].

mitogen
25-05-2006, 02:39
^
yeah i always use it for potentiation cause its the cheapest thing around in holland however in france its fricking expensive (1 euro here)

i took like 40 mg doses with say codeine and it really helps it along

however in those kind of doses it can be very bad for you and damage the intestines i found out the bad way although i never had a doctor check it out.


and it doesnt work that way jcrest , maybe 30 mg of loperamide equals 20-40 mg of codeine in the head but like 400-500 in the body without the histamine release.

however its very good for potentiating when taken a bit before the other opiate the loperamide will fill up the opiate receptors in your body so more of the good opiate will go to your brain.

however i think with your prices it aint wort it

i like it because is potentiation without interference like with a benzo or an antihistamine

I understand the mechanism by which you propose that loperamide potentiates other opioids - same reason they add carbidopa to L-dopa: the carbidopa doesn't get into the brain so it works nicely for competing with l-dopa at somatic enzymes.

On a scale from 1-10 (where 1 is nothing and 10 is, say, a doubling of efficacy) how would you rate the effectiveness of a.) a therapeutic dose, b.) twice the therapeutic dose and c.) a massive dose like you have been talking about - say 40mg?

To be honest, considering the price of loperamide in the form of immodium (perhaps a prescription could be cheaper,) its probably easier and more constructive to simply go find some more commonly used opioids.
However, if anyone does happen to find a supply of quinidine, I'd love to hear the results. As I mentioned, we've discussed this before, and nobody really tried doing anything. That quinidine study does look interesting, for sure.

johanneschimpo
25-05-2006, 02:43
your scale isn't built for a tripling of efficacy :o

BingeBoy
25-05-2006, 02:52
^mitogen
forget the therapeutic doses

however from 15-40 mg onwards it will have a noticeable effect like 1-3 i think on your scale ( a normal benzo dose will be 10 cause it makes me halve my opie dose )


im not good with the numbers but lets say its one of those things that makes a dose of codeine under 300 mg worthwhile e , greatly adds to the itch and actually gives me opiate pupils instead of very slighly contracted pupils in this setting it also makes me itch. 300 mg of codeine on itself wont maybe the first day i havent been using opiates for a few months now.


however what i would like to state again and a reason why i like it (i dislike antihistamines for instance and will only add them to the mix if absolutely necessary even though those have a shared pathway or something) is that it doesnt taint the opie feel and seems to add to euphoria rather than sedation.

ps this bit is from the cold water world potentiator page (http://adhpage.tripod.com/potentiators.htm) :

26. Loperamide (Immodium): This drug is related to meperidine/pethidine (Demerol) but does not cross the blood-brain barrier in sufficient quantities to cause euphoria. However, the consumption of doses of 150-300% of the therapeutic dose when mixed with high doses of codeine or meprobamate have been reported to produce a weak Darvon-like buzz aside from the effects of the other drugs.

almost-
25-05-2006, 19:45
Actually PGP inhibitors are commonly found in nature, for example black pepper(1) and garlic(2) contains some.

And I can tell you that >32mg doses with PGP inhibitors really work like an opiate.

1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12130727&query_hl=15&itool=pubmed_docsum
2.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11466175&query_hl=12&itool=pubmed_docsum

jasoncrest
26-05-2006, 01:10
And I can tell you that >32mg doses with PGP inhibitors really work like an opiate.

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.

jasoncrest
26-05-2006, 01:26
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?)]

mitogen
26-05-2006, 03:45
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?)]


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.

BingeBoy
26-05-2006, 12:06
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

mitogen
27-05-2006, 07:38
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

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

jasoncrest
27-05-2006, 16:50
quinine as in schweppes doesnt work

Really? Why Not?


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

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.

Survival0200
27-05-2006, 18:07
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.%)

BingeBoy
27-05-2006, 18:56
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.

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.

TheTripDoctor
31-05-2006, 04:46
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?

DrEIMiller
31-05-2006, 20:01
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%20Brand%20names,%20T rade%20names

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?

DopaMan
01-06-2006, 01:53
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.

DopaMan
01-06-2006, 01:58
^^^ 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 :)

5-HT2
02-06-2006, 06:39
I don't know whether to laugh or cry over the subject matter of this thread :\ 8)

Survival0200
02-06-2006, 07:16
I don't know whether to laugh or cry over the subject matter of this thread :\ 8)
Why?

"Discussion of journal articles, drug science and other theoretical topics"

yaesutom
02-06-2006, 16:38
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..

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..

Smyth
02-06-2006, 19:36
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/query.fcgi?cmd=Retrieve&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.

TheTripDoctor
03-06-2006, 21:45
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 :)

kakti
05-06-2006, 16:18
MPPP was the desired analog, and MPTP was the accidental analog produced by heating the solution too quickly at too high of a temperature

norco10
05-05-2008, 02:52
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.

The Monkey Mantra
05-05-2008, 03:06
Fuck it, take the whole 100. I ate 96 mg of loperamide with no tolerance to any narcotics and definitely felt peripheral effects. Centrally, I was relaxed, but the frog-in-my-throat opiate voice definitely came out. I wasn't high, really, but I slept very well.

norco10
05-05-2008, 03:18
did you take quercetin with it. aI;m feeling a bit strange right now i woud have taken the wholw 100mg but did not wany to over dose in case the quercetin worked in a hour I will take a booster og 40mg if I fee normal

norco10
05-05-2008, 03:40
took a boster of 40mg and I am feeling more of a disasocative effect than an opiate high though I have a small opiate high

negrogesic
05-05-2008, 05:40
Unfortunately, I have tried doing this various times, with 500-750mg quinine and 60-100mg loperamide, as well as 300mg and 450mg quinidine (quinidex ) with 80mg and 70mg of loperamide respectively. Bottom line: i felt very little, and what I did (the 450mg quinidine + 70mg loperamide was most noticable) was extremely shitty in quality. This is incredibly stupid, and anways, when loperamide is forced across, the effects are very dirty.

haribo1
05-05-2008, 09:09
Loperamide has been shown to dehydrate in the body forming a neurotoxic MPP+ type substance. Put me right of trying anything silly.

Accept that you will have to do a little chemistry and it will pay off. Swap the bare -OH for a halogen then use NaBH4 to strip said halogen AND that chloro group.

According to the patent, you now have a product some 40x stronger...

norco10
05-05-2008, 11:57
Loperamide has been shown to dehydrate in the body forming a neurotoxic MPP+ type substance. Put me right of trying anything silly.

Accept that you will have to do a little chemistry and it will pay off. Swap the bare -OH for a halogen then use NaBH4 to strip said halogen AND that chloro group.

According to the patent, you now have a product some 40x stronger...

well noted I am dehydrated as fuck, i have had a gallon of gatorade in the past 4 hours stil it will not quince my thirst. Never again.

MurphyClox
05-05-2008, 17:56
Unfortunately, I have tried doing this various times, with 500-750mg quinine and 60-100mg loperamide, as well as 300mg and 450mg quinidine (quinidex ) with 80mg and 70mg of loperamide respectively. Bottom line: i felt very little, and what I did (the 450mg quinidine + 70mg loperamide was most noticable) was extremely shitty in quality. This is incredibly stupid, and anways, when loperamide is forced across, the effects are very dirty.
I tried practically the same and the only thing I felt was the fucking tingeling in my ears for 2 days (...chinine sideeffect!). This is a shitty idea indeed. Adding potential neurotoxicity makes it even shittier!

major13
05-05-2008, 18:56
hmm.. well I don't know if it has been mentioned in this particular thread.. but, Paxil (paroxetine) happens to be a pgp inhibitor, comparable in it's efficacy to that of even quinidine. At least, according to some research. There's a thread somewhere asking a willing participant to experiment with the combination. I would.. but I have about 50mg of Paxil.. I doubt that would be enough. What do you peeps think?

MurphyClox
05-05-2008, 22:36
quinine as in schweppes doesnt work

Really? Why Not?
...because the quinine content is FAR too low to be effective. It's only used to render the flavour bitter, as quinine is one of the most bitter substances known. And because it is THIS bitter, the contained amounts are extremely small.
Quinine is also used as agent against muscle cramps but the required amount of Schweppes to see a effect on cramps would be +10 l. So: Schweppes is useless here.

Isn't anybody scared by the possibility of dying after Loperamide consumption?! Strong dopaminergic neurotoxicity, then Parkinson-like symptoms, death within days or some weeks. Alternative: Taking Parkinson-medicine for the rest of your life and possible brain damage... Plz think about it before you cry I TEST IT! I TEST IT. Plz!!!

Stay safe! Trip but stay alive!

Murphy

vecktor
05-05-2008, 22:47
why will the loperamide BBB threads never die.

getting Loperamide across the BBB is an extremely stupid thing to do.
quinine is quite cardiotoxic too quinidien is more so. though whilst this isn't as good as the superglue insulin method proposed by another wannabe loperamide ingestor, it is very stupid.


Parkinsons is for life not just for Christmas.
Unless someone comes up with some safety data that shows that the animal studies are wrong and loperamide doesn't cause MPP+ haloperidol type DA neurotoxicity then leave this well alone.