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Loperamide and MPTP dangers

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BretdaBoxer

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Jun 12, 2016
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Ok, this may have been posted before but unfortunately for anyone that cares im not willing to search around forever to find out, so I'll ask myself.

Ok i hope someone can help me here. I just switched off 100mgs of methadone for 4 years to 2 suboxone 8mgs a day. It was the hardest thing i did as for the first 3 days the suboxone was still being blocked by my methadone clogged receptors. Here i am 3 weeks later and still suffering from lazyness and weakness. I still have the lingering withdrawals. I found on the internet about loperamide and it seemed like a miracle. I switched from suboxone to loperamide 80mgs once daily. Now the suboxone isnt working again and this is the first ive read about possible arrhythmia from loperamide. Im really athletic and i love to box and run. I dont want to have a heart attack while im sparring at the gym. "Seen a 40 year old man have one and die in the gym last year." Now im going to immediately start coming down off this loperamide and try to switxh back to this worthless suboxone. If anyone can weigh in and tell me the risk factor here if u know. Im 26 years old im 6'2 about 200 pounds. Im extremely athletic and i use my heart daily as i do sprints and all out sparring daily.

Also i have read that loperamide and MPTP goes hand in hand but you are safe because it doesnt cross the bbb or cns or whatever. (Probably not a fact but im not a wiz like u guys.) Does this mean in high doses such as 80mgs it can cause parkinsons?

Am I in direct danger of parkinsons or arrhythmia?
 
OK, I don't have anything to go by but personal experience, but I've been taking 200mg loperamide daily for my own maintenance for over two years now with no problems, not even constipation. Blurry vision occasionally if I take too long to dose. I also walk miles every day (loperamide actually helps with this, takes away fatigue). I've got two other people on similar regimens, one almost as long as myself. I have another friend who knows it works, but read about "sudden death" online and got scarred away, and does heroin instead (I told her, "hey, FWIW, 'sudden death' is also a side-effect of... duh... heroin!") I think the heart irregularity is that with common opioids; slowing of heart rate etc. I haven't had any permanent parkinsons like symptoms at my dose; though once I took over a gram in 48 hours and it messes your ability to walk erect way up. But it's temporary (or was for me). So that's my two cents.
 
MPTP is not a metabolite of loperamide, if it was, loperamide would never have made it to market. MPTP will convert to MPP and will cause parkinsonism.

You are referring to LPP -- a metabolite of loperamide that is similar to MPP, but has difficulty crossing the BBB. There is no body of evidence regarding LPP, then again, nobody EVER thought opiate addicts would down boxes of anti-diarrhea meds.
LPP is tied to p-glycoprotein and as such has significant difficulty crossing the BBB. LPP is theoretically less toxic than MPP. Do you want to take the chance?
 
But do other opiates like methadone metabolize to LPP? And yes it seems crazy but its diarrhea medicine because its a opiate and like any other opioid it constipates u. So the word diarrhea medicine posted on the bottle does not bother me. What does bother me is the possibility of longterm damage. I tell u it seemed like a miracle at first that i can just go to walmart and not be sick. The asshole doctors are no longer like gods to me. It looks like ill bengoing back to the suboxone dr and extend the time it will take to get my CDLs for my job. They dont let truck drivers if they are prescribed opiates. However the opiates do not effect me with drowsiness anymore. 38 an hour is on the table if i stay on the loperamide. No money is worth perminate damage.
 
BretdaBoxer said:
But do other opiates like methadone metabolize to LPP? And yes it seems crazy but its diarrhea medicine because its a opiate and like any other opioid it constipates u. So the word diarrhea medicine posted on the bottle does not bother me. What does bother me is the possibility of longterm damage. I tell u it seemed like a miracle at first that i can just go to walmart and not be sick. The asshole doctors are no longer like gods to me. It looks like ill bengoing back to the suboxone dr and extend the time it will take to get my CDLs for my job. They dont let truck drivers if they are prescribed opiates. However the opiates do not effect me with drowsiness anymore. 38 an hour is on the table if i stay on the loperamide. No money is worth perminate damage.
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No other opioids are known to have neurotoxic metabolites.
 
Wrong, serotonin2A. Norpethidine is toxic.

Don't know the kinetics of the efflux pump that spews it back out (AFTER it crosses, as I understand it, is this wrong?) that would mean if it IS overwhelmed by megadoses of loperamide (A GRAM?jesus fucking wept man! if thats what it takes to keep going...your not gonna like it when you come off that! good luck keeping your sphincters where they were intended to be without resorting to corks and superglue:P

And the user who said that smackheads scarfing loperamide by the gram.

And morphine does as well. Morphine-3-glucuronide is NASTY stuff, induces a whole load of proinflammatory cytokines and such. Especially with spinal administration of morphine. But some exposure nevertheless. And damned if I can't agree with what that infers the effects on the body would be, at high doses of morphine (1g shots IV of morphine sulfate as either pharmaceutical MS, or poppy isolate, although that gets saved for higher purposes than just shooting as it is, minus the codeine, given the limited quantities ever available to me; propionyl-papavaretum is where it's at man!)
 
I took higher doses than 80mgs regularly also but whoa not a gram. It seems there's a wide swing between effective doses which is why so many dispute its efficacy. I did notice that tolerance developed quite rapidly and with each return to use or close dosing the symptoms intensified to the point where chest pain was alarming enough to make me quit and then.....oh be ready as it was by far the worst wds I ever had. Also because it jacked up tolerance and had such a long half life it was impossible trying to rescue myself with mega doses of other opioids. It took two weeks of hell and no drugs whatsoever to even begin to feel a dose of IV dilaudid. No joke. I would switch to something else sooner rather than later. My experiences were enough to say that's one opioid I will never touch again.
 
It does not constipate me and i dont know who said anything about a gram. Thats 1000mgs? Thats like 10 bottles... U would have to be ignorant or downright depressed to try that. Some would say that about 80mgs tho. Im trying 3 doses of 10mgs today along with my 2 suboxone a day. Tmrw ill cut it to 9mgs until i reach 0mgs. The halflife should keep me from having issues hopefully.
 
LPP, being a quaternary ammonium cation, is unlikely to cross the BBB even if it's not pumped out by PGP. The problem with MPTP is that it does cross the BBB, and is metabolized into MPP+ in the brain. Since loperamide doesn't get into the brain, the same scenario is unlikely even if loperamide is metabolized into such a substance.

However, this still doesn't mean that high doses of loperamide (>50 mg) are safe to take daily.
 
The evidence isn't quite clear but I personally would stay away from using loperamide as a long term maintenance drug until more is known about it. It appears that it poses more risks than most other opioids. The possible heart problems from loperamide don't really appear to me the same as other opioids at all actually, typically the danger from most opioids is respiratory depression which would lead to heart failure when the user dies from respiratory depression.

People who have overdosed on loperamide have apparently died directly from heart issues from what I have read. Correct me if I'm wrong.
 
Ligaturd said:
The evidence isn't quite clear but I personally would stay away from using loperamide as a long term maintenance drug until more is known about it. It appears that it poses more risks than most other opioids. The possible heart problems from loperamide don't really appear to me the same as other opioids at all actually, typically the danger from most opioids is respiratory depression which would lead to heart failure when the user dies from respiratory depression.

People who have overdosed on loperamide have apparently died directly from heart issues from what I have read. Correct me if I'm wrong.
Click to expand...

Yes, my lil research indicated that multiple people have heart arrhythmia from taking mega doses of it. Im "only" taking 30mgs now. Im about to go do sprints and jog. Its alil concerning but i think ill be alright. Ive had a amatuer boxin match while on 100mgs oral and 100mgs iv of methadone at the same time, and that didnt kill me. (A verrrry bad idea looking back, but they make me feel invincible). Ill be damned if 30mgs of this takes me down lol. I deffinately am tapering off this because the intense cardio i do daily may bring on bad symptoms from this. Idk we'll see. I appreciate all the input.
 
Limpet_Chicken said:
Wrong, serotonin2A. Norpethidine is toxic.

!)
Click to expand...

I said it wasn't neurotoxic, as in causing death of neurons. All opioids are potentially toxic if you take a high enough dose, ie you will stop breathing. Norpethidine has excitatory effects but it is NOT neurotoxic.
 
Not all neurotoxins cause neuronal deaths, other than via secondary causes, like death of the organism, hypoxia etc via e.g aspirations
 
All the posters so far are correct on their assessments of why of why LPP shouldn't be an issue. p-GP induced removal, etc. However.

This is all based on the idea that loperanide does not cross the BBB.

And we all know, at this point, that this is a shaky claim to stake.

I refuse to believe that the efficacy of high dose loperamide [as a miracle 'cure' (more like a band-aid) for opioid withdrawal, and to the mu-naive, a recreational drug] lies solely in it's ability to stimulate opioid receptors in the PNS.

There are also those many people who attempt to increase effects through inhibition of p-GP.

In one study, cited around here ad nauseam, it is clear that some of these inhibitors work effectively enough with loperamide to allow for CNS depression to occur.

So whether an individual is just simply overwhelming the appropriate transporter by taking a large dose of the substrate, or inhibiting the transporter to allow for enhanced action of the substrate, it is sound at this point, my friends, to tentatively accept that loperamide crosses the blood brain barrier, although not at normal doses, and not very efficiently even at higher doses.

Then, the question is begged: What if LPP is created IN the brain, and given charge to LPP+ from WITHIN the BBB, and the p-GP is already overwhelmed to a point of effectual failure...what now? In this theoretical situation, we now have quaternary amides and charged particles being made from WITHIN the brain, and since p-GP is overwhelmed, no real way to efficiently get them OUTSIDE the brain.

I am not going to go into all the problems with OPs assumptions about buprenorphines pharmacokinetics and the way it competitively binds (methadone and loperamide will NEVER "block out" buprenorphine from a given mu receptor. Ever.)

But I think that the topic of this thread is an interesting one, and although I may be wrong, It is my opinion that there is actually not enough literature in HUMANS available to say that the theory can be debunked OR confirmed, at least with any degree of fair certainty.

Remember, that liperamide arrhythmias are known to go away, even after switching to other opioid like methadone and buprenorphine, both of which (although the former in particular) are known to cause arrhthymias via elongation of cardiac QT interval.

Meaning; loperamide seems to be at least more cardiotoxic than methadone. By what degree, I can not say.

But something to keep in mind if you are planning to be using loperamide as a long-term ORT.
 
Limpet_Chicken said:
(A GRAM?jesus fucking wept man! if thats what it takes to keep going...your not gonna like it when you come off that! good luck keeping your sphincters where they were intended to be without resorting to corks and superglue:P

And the user who said that smackheads scarfing loperamide by the gram.
Click to expand...

That was only once, recently out of prison. And I had to get narcan'd 5 times over a 24 hr stint in the ICU 'cause I fell out; no other opioid in my system. A gram is not a recommendation, it's just the most I've taken. 200mg a day works for me.
 
Limpet_Chicken said:
Not all neurotoxins cause neuronal deaths, other than via secondary causes, like death of the organism, hypoxia etc via e.g aspirations
Click to expand...
The dictionary definition of "neurotoxic" is "poisonous to nerve tissue, as to the brain or spinal cord". Based on that definition, normeperidine is not neurotoxic. It certainly has excitatory effects but it is not physiologically toxic or poisonous to nerve cells (it doesn't kill cells or derange normal physiologic processes such as cell respiration or transcription/translation).
 
Which opioid exactly is metabolized into MPTP? MPTP may be a by-product of desmethylprodine synthesis, perhaps pethidine as well if it's not done properly, but as far as I know it's not a metabolite of pethidine or any other opioid, it wouldn't make sense clearance-wise. And what is LPP exactly? It doesn't seem likely either that loperamide might be dehydrated in vivo to a metabolite that is MPTP-like.

What stroke me though are those high doses of loperamide that some people are taking, I was surprised one could use loperamide as a working aid for withdrawal, now maintenance? 200mg/day? Isn't this by chance more expensive than generic Subutex?

http://www.annemergmed.com/article/S0196-0644(16)30052-X/abstract
http://www.hindawi.com/journals/crim/2016/4061980/
http://www.tandfonline.com/doi/abs/10.3109/15563650.2016.1159310?journalCode=ictx20

The risk appears to be real.
 
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