Opioids As promised-Prozac and it's effect on Loperamide.

While doing research for an answer, I stumbled upon an excerpt, that claimed prozac inhibited p-glycoprotein, thus allowing loperamide to cross the bbb.

Here is the excerpt from wiki: Fluoxetine and norfluoxetine inhibit many isozymes of the cytochrome P450 system that are involved in drug metabolism. Both are potent inhibitors of CYP2D6 (which is also the chief enzyme responsible for their metabolism) and CYP2C19, and mild to moderate inhibitors of CYP2B6 and CYP2C9.[55][56] In vivo, fluoxetine and norfluoxetine do not significantly affect the activity of CYP1A2 and CYP3A4.[55] They also inhibit the activity of P-glycoprotein, a type of membrane transport protein that plays an important role in drug transport and metabolism and hence P-glycoprotein substrates such as loperamide may have their central effects potentiated.[57] This extensive effect on the body's pathways for drug metabolism creates the potential for interactions with many commonly used drugs.

I would like to get bler's take on this. Why it would/wouldnt work. Can it be used for other drugs, such as buprenorphine?

If youre prescribed prozac and have ever taken lope with it, your feedback is greatly appreciated. First hand experience will outweigh theories here. However I dont want people running out to get prozac, it has dangerous side effects, and unless prescribed, I will not endorse it's use. By giving a first hand account, you must agree that you are prescribed, and this will be assumed by the readers.

Looking forward to your guys' opinions and theories!

SpeedKing and 7nos SS373dOH

Regarding the buprenorphine, Prozac won't inhibit the metabolism too much I think (iirc it's metabolized by CYP3A4 into norbuprenorphine and that's what you want) but the inhibition of P-glycoproteins will result in norbuprenorphine penetrating the BBB better, so it should make you 'higher' given that norbuprenorphine is a full mu-receptor agonist.

Regarding the lope. Yes lope should penetrate the BBB better, so you maybe can get high off of it, but the problem is, as far as I know no one knows the potency of loperamide, so by inhibiting P-glycoproteins you get an unknown amount of loperamide into your brain and you don't know the potency of it. I once read a paper not to long ago stating that loperamide is more potent than morphine, I think it was around three times as potent, but I could be wrong.
If people who don't have a tolerance take this Prozac loperamide combo it could be lethal.
And iirc the paper stated that naloxone didn't do much, so what if loperamide has a really high affinity for the mu-opioid receptor and naloxone won't do shit if you OD on it?

Imo it's not worth the risks.

kleinerkiffer , I heard the same thing about loperamide possibly being as strong as Fentanyl. The purpose of this thread is for theoretical information. A lot of research has to be done concerning loperamide in general.

According to various postings and threads on this site pertaining to loperamide, loperamide is heavily misused and abused by many people. One of our purposes of this thread is to shine light on how it works, just how dangerous it is and if it is to be properly researched, then researched safely.

This thread is very serious. To anyone reading this thread, it must be understood that this is to be treated as it were fentanyl. There is the distinct possibility that this drug may be active at sub milligram doses. Study at your own risk.

^ Exactly

People have been trying to use a p-glycoprotein inhibitors, in various strengths, to megadose loperamide. The only reason to megadose, is to "push" passed the bbb, this is a layman's misconception. It does pass the bbb, however it is immediately transported out, by p-glycoprotein. By inhibiting this, megadoses become dangerous. There isnt yet proper doses for this, I think establishing a safe, effective dose, might not be a bad idea.


- Hopeless

Why establish a dose? Loperamide isnt intended for CNS activity and with the added danger of cardiac toxicity, who would want to investigate this when we have other drugs to do the job.

^ So people who do end up doing it, have a.starting point, and dont od. But the thread isnt based soley on lope, any other drug that has bbb trouble can be discussed. Thx for your input though!



- Hopeless Soul

I dont think fluoxetine is the worst SSRI to combine with loperamide though. Sertraline and paroxetine seem to be much strong pgp inhibitors on par with quinidine or verapamil. One study I read, the levels of digoxin that passed the BBB were not affected at all by fluoxetine in rats (maybe mice). And it is generally listed as a moderate pgp inhibitor. Now if you are taking like 700mg of loperamide a day, I doubt you would even need to inhibit pgp to get an effect and doing so is a recipe for disaster be it a weak or strong inhibitor.

7nos, have you ever read case studies of people who presented with loperamide toxicity? They are not fun and urge everyone to consider other options before using loperamide for recreation or to combat withdrawal.

I will try to add some info about other drugs when I get a chance, too.

^ Thanks for adding knowledge to the thread, and yes i read some of those studies, what I was thinking is maybe we can elimante some of those cases, and megadoses in general by researching this pgp inhibitor topic.




- Hopeless

Oh yeah, if you have any other info or links, post away!


- hopeless

If anyone else has any other drugs, that get flushed out of the bbb, by pgp, feel free to post them. We'd like to cover a variety of substances, not only loperamide! Thx in advance!


- Hopeless

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC539326/table/t1/

Here you go, plus a bunch of other transporter substrates and inhibitors.

And here is FDA's current guidelines on the drugs to use as substrates, inhibitors, and inducers of all types of stuff

http://www.fda.gov/Drugs/Developmen...teractionsLabeling/ucm093664.htm#PgpTransport.

Study of lots of antidepressants and pgp including some metabolites. Bit old but not that bad.

http://jpet.aspetjournals.org/content/305/1/197.full

Last one, I swear. Quarter million elderly patients analyzed for digoxin toxicity in combo with SSRIs. Conclusion, there is no clinical relevance.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1884963/pdf/bcp0059-0102.pdf

^ Thank you so much kitty! Feel free to post more links or your theories in this thread. From the posts I have read from you, you seem to be quite knowledgeable, so your input is quite valued here!



- Hopeless soul

Let me be perfectly clear though (hence new post). Just because the SSRIs may or may not be very strong inhibitors of Pgp, I still would not combine them with large doses of loperamide as nearly all SSRIs have been linked to QT prolongation which can lead to tosade de pointes and sometimes death. Loperamide also can do all this, so please lay off this combo. In fact, lay of big doses of loperamide. I know it is cheap and available but if you are suffering from withdrawal, either find a safer route or fight as hard as you can to get through it. And if you use loperamide to get high, well, I hate putting any drug use down, but c'mon now. Either find some real shit (not suggested) or just get out of the game.

7nos-SS373dOH said:

^ Thank you so much kitty! Feel free to post more links or your theories in this thread. From the posts I have read from you, you seem to be quite knowledgeable, so your input is quite valued here!



- Hopeless soul

Click to expand...

Thanks, I try. There are better scientists than me on BL but Im here more than them. Fortunately, Pgp has been studied quite a bit so we can make some guesses and how drug that affect it will affect actual people. Read through that FDA link. They have only in the past few years begun exploring the vast array of transporters in the human body and making the pharmaceutical companies exam their new products for how they interact with them and produce drug-drug interactions. And since CYP450 and transporters are often intimately linked, it is amazing how the real scientists are able to discover anything about how drugs move through the body.

^ Yes! The "new gen" of opioids will be quite effective! I read an article about some of them, and im excited to say the least, if I can dig up that article, I will post the link. We're on the forefront of discovery too, its exciting to be a part of, you dont need to be a scientist, to push the forefront of discovery, in the substance world. Just think of all the things addicts have discovered over the years! From the effect, or lack thereof, of naloxone in suboxone, to cold water extraction. And yes, I'm in the midst of reading it now.


- Hopeless 7nos