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Forcing Loperamide through the BBB

well extract them as you would codeine from a tylenol 3, or psuedophedrine or hydrocodone, or alprazolam. ive never done it but it can obviously be done. and i dont know the magic. i wouldnt know where to start, even designing the drug. im not familiar with opiate molecules at all. im just saying, it might be possible to alter the chemical structure a bit so that it passes through, and is also an opiate still.....

maybe turn that alcohol group into another ketone???...would be pretty easy chemistry ;0
 
this still doesn't alter the fact that there is evidence to suggest loperamide has the potential to do some really nasty things in the brain.

don't go there, just find something else to play with.
 
ahh its tertiary sorry didnt really put that through my head.

vektor, i do believe you but i cant find much info on chems with similar structures to loperamide, what makes you think it has potential for doing damage?
 
I have personally taken 16 to 32 mg of Lopermide and it does help with Opiate Detox, I have never used it in conjunction with other things such as Quinine. The Lopermide by itself helped a TINY Bit but when I took some before floating some Oxys it made them much stronger and long lasting.
 
sackynut said:
ahh its tertiary sorry didnt really put that through my head.

vektor, i do believe you but i cant find much info on chems with similar structures to loperamide, what makes you think it has potential for doing damage?
Click to expand...

haloperidol for one, which is known to be neurotoxic.
also MPPP (pethidine reverse ester), which is another one of these tert alcohol piperidines, here the alcohol group is esterified. of course there is the notorious by-product MPTP (instant parkinsons)

Then there is the ability of loperamide to cause neurotoxicity in animals with incomplete BBBs, there has been a large amount of discussion here about it, use the search engine.

there are a few studies where loperamide has been used in humans with trickery to get it through the BBB, rather to overwhelm and avoid it being pumped back out by the brains detox mechanisms. None of these studies looked at DA neurotoxicity how they got the study past the ethics and safety group I don't know, the problem as I see it is even if it isn't as effective as MPTP at nuking DA neurons, it could still show effects later as normal ageing causes loss of DA neurons resulting in parkinsons (which is of course currently incurable)

just buy poppies.

there are too many flashing warning lights, sometimes discretion is the better part of valour,
 
define dopaminergic..

it should be similar to haloperidol, loperamide would be expected to have central dopaminergic effects, probably through DAT , more likely though the metabolites derived from removal of the alcohol to a tetrahydropyridine like LPP+ (which cannot leave the brain once it is formed due to a a permanent charge) would be transported by DAT however this is not a good thing.

I have a hypothesis that loperamide threads seem to attract a disproportionate amount of lazy stupid people. Would people go away and do some reading and better still some thinking before posting about loperamide/ the purpose of ADD is to have high level discussion, which kind of implies that the poster has read the openly available literature before posting. google search is a good start...
try
.....effective therapy for diarrheal illnesses (Sherman
and Fish, 2000). A likely explanation for the lack of CNS toxicity
of loperamide as opposed to MPTP and haloperidol is the well
established P-glycoprotein substrate properties of loperamide that
restrict brain penetration and prevent bioactivation of this drug in the
brain (Mahar Doan et al., 2002; Wandel et al., 2002). This proposal
also aids in explaining the absence of central opiate effects of loperamide
Click to expand...

http://dmd.aspetjournals.org/content/32/9/943.full

go read the referenced papers please.

I will not respond to any further threads or posts discussing loperamide unless it is clear the poster has read the available literature and bothered to think about it. that means citing references.
loperamide has been discussed again and again on ADD, and each thread is like some wierd deja vu.
 
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vecktor said:
(which cannot leave the brain once it is formed due to a a permanent charge)
Click to expand...

Well, could we do that as the opposite of loperamide in some capacity with another substance altogether, then?

Are there opiates which, instead of not crossing the BBB from the external, could become so charged as to inhabit the brain for longer periods until metabolized (and not work on then non-analgesic periphery receptors which cause constipation and such unwanted side-effects) and remain on the internal side of the BBB?
 
Are there opiates which, instead of not crossing the BBB from the external, could become so charged as to inhabit the brain for longer periods until metabolized (and not work on then non-analgesic periphery receptors which cause constipation and such unwanted side-effects) and remain on the internal side of the BBB?
Click to expand...
No.

Loperamide is not going to become centrally active through any sort of chemical modification. Even if you do devise some way to make nanoparticles in your basement, PEGylate them, and IV, you're risking massive toxicity.

Vecktor is right, just buy poppies. This thread should die a quiet death.
 
if you guys think this thread is bad you should check out the same thread over at drugs-forum.uk ;) i haven't seen it in years but i'm sure it's still going strong... lol
 
I'm with Vektor on this one, its not worth the risk of forming fucking MPTP-like compounds!

This is a harm reduction site, that's why I'm here. Its ridiculous that this is even being discussed after the possibility of MPTP -like byproducts being formed was discussed.

Granted I've got a raging hate for almost anything that can cause Parkinsons :\
 
I wasn't talking about loperamide. It would have been clearer had I said - No, the blood brain barrier doesn't work that way.

There's 2 ways to get things across the BBB - active transport and diffusion through the cells. The former is used by a few things like sugars and amino acids but is compound-specific, and the latter is what almost all psychoactives rely on and is based on fat solubility. Forming salts or other charged species of drugs decreases the fat solubility of the drug by increasing polarity. The real problem is that there's no way to 'force' a drug to stay behind the BBB without relying on some sort of metabolism that is brain-specific, and few drugs are metabolized only in the brain.

Hpwever there are also issues with molecules being too large, or being actively transported out of the brain, as seen in loperamide.
 
I think loperamide with a PGP inhibitor would work fine. I think reasonable doses, < 100mg are actually fine. I went up all the way to about 170mg in a day and I slept for like 36 hrs straight and I had a terrible headache. I then was able to moderate mild WD with about 30-40mg every 10 hrs or so. I then took gabapentin 3g after a week break and I feel FANTASTIC. This is a great drug.

So my conclusion is that both loperamide and gabapentin in high doses are really good to handle opiate WD blues, i.e., post acute withdrawal and mild physical WD (but do not take it together since it doesn't work like that).

The reason I am trying out loperamide and gabapentin is that I came off the fentanyl 50mcg/hr patch. I was able to taper down and get off successfully but I had this nagging feeling that is "fixed" by taking gabapentin or loperamide at the doses listed above (first it took me 120mg, then 170mg which was too much, and then I just took 40mg and 30mg doses which keep my mood sane until I lost my tolerance to gabapentin and then I switched from loperamide to gabapentin). This approach seems to work very well

I will get new fentanyl in a week.
 
This is awful...I hate this subject but I can't look away...I just read ALL FOUR PAGES of this crap!!
 
PGP inhibitors seemed to be the only way I had effect. Zoloft and cimetidine, along with as little as 24mg of loperamide, had me feeling warm, cozy, and floaty. Very nice. Haven't been able to replicate the experience since getting off the zoloft. Just got back on it, maybe I'll give it another go in a month or so.

Somebody said that gabapentin might inhibit the effects of loperamide. Last time I tried lope I had been on gabapentin and had absolutely no effect from the loperamide (besides not pooping for about a week).
 
Many chemicals function as pgp inhibitors. Here is a short list:
Amiodarone
Clarithromycin
Cyclosporine
Diltiazem
Erythromycin
Indinavir
Itraconazole
Ketoconazole
Nelfinavir
Nicardipine
Propafenone
Quinidine
Ritonavir
Saquinavir
Tacrolimus
Tamoxifen
Verapamil
from "Life-threatening Colchicine
Drug Interactions"
by John R. Horn, PharmD, FCCP, and Philip D. Hansten, PharmD. Pharmacy Times, pp. 111, May 2006.

The obvious problem of course, is that pretty much all somatic cells have Pgp trans-membrane transporters, and there are likely just as many kinds of PGPs as there are tissue types. Just because a drug may effect one pgp, it is unlikely to affect all of them. I suspect those in the BBB will be especially difficult to manipulate. I suggest discussing with a cell physiologist. I know a few, but I don't want to them to think I a junkie! Really I'm not (tho I used to be), this is all just interesting to me.

What you need is something that quickly induces the transporter or relaxes the barrier junctions for entry, then closes the barrier, trapping loperamide behind. Has anyone considered amyl nitrite (i.e. poppers)? Its very fast acting barrier. More importantly though, its effects wear off rapidly. Its been tried in similar BBB experiments before.

As a fairly safe trial, take like 10 mg Lop, wait 30 min, then hit a popper once or twice and see how it goes for the next hour. If you survive, report back. JK. This is a safe experiment, I think.

Disclaimer
you might die, but probably not.
See, "Brain barrier systems" By Ábel Lajtha . I think its available on google.books
 
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