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will 5ht2b antagonists lessen heart valve/pulmonary damage in combination with amps?

L

lightn!ng

Greenlighter
Joined
Aug 29, 2010
Messages
7
Are there any 5ht2b antagonists that would lessen or even prevent valve/pulmonary damage when administered in combination with amphetamine, methamphetamine, or mdma?

The only such antagonist I have on me is mirtazapine, but somehow I doubt it would be effective...

thoughts?

Thanks BL.
 
bump. surely someone can shed some insight?

I thought it might be an interesting idea for harm reduction, but would like to hear from someone better informed.
 
Don't bump your own thread... this is a forum and as such, people respond when they read the post, not when you want them to. Furthermore, bumping your thread is impolite and impatient and might discourage potential posters.

I don't know the answer and likely not a lot of people who post here will so IF someone can answer this, it may take some time.

I do know that MDMA is a non-selective 5HT agonist so combining a 5HT2b-selective antagonist will negate certain MDMA effects but I can't comment on how this will overall change the feel (if it really will at all).

Unfortunately, I don't know the character or extent of pulmonary damage caused by amphetamines and phenethylamines so I'm not sure if there any 5ht2b antagonists that would mitigate these effects.

edit:

wow I just saw that the OP was over a month ago, usually self-bumpers are within a short period after the first post so I apologize for part of my response. The general rule is "don't bump your own thread" but after no answers in a month, I don't really see a problem.

I'm not sure if anyone who posts in OD will be able to answer this, but I don't have a problem giving it another chance.
 
Thats okay Cane, I'm actually a little surprised at the lack of response myself... I genuinely thought this was an interesting question and that others might be curious as well, but I guess not.

Possibly, might the knowledgeable folks on ADD have some ideas? I dont feel comfortable posting this there for obvious reasons.
 
I'd imagine ADD might be a better place to post this question. The regulars there are great at handling these questions. I take amphetamines myself but I've never considered what effect 5HT2b-selective antagonists might have on cardiopulmonary damage. Interesting question!
 
5HT2B receptors in the brain seem to be crucial for at least some MDMA effects, as brain penetrant 5HT2B antagonists block the effects of MDMA in animals (see J. Neurosci., Vol. 28, No. 11. (12 March 2008), pp. 2933-2940.)

However note that there are some 5HT2B antagonists with very poor blood-brain barrier penetration and it seems likely that these would be useful for combating 5HT2B-mediated heart valve damage if they were taken alongside MDMA or other serotonin releasers or 5HT2B agonists, and hopefully without affecting their action in the brain. Not sure whether any existing agents are really suitable for human use though...
 
I don't think there are a lot of really truly selective 5HT2B antagonists, most of them are also 5HT2A/C antagonists too. The only super selective one is RS-127,445, which was used in the MDMA paper above, but the safety of that falls under who-knows-what. The 5HT2B receptor is targeted by pretty much all psychedelics too, so it may contribute to some of the psychological effects of the drug as well. I don't know if there's been any studies in humans testing this.

The best thing to do is just to avoid serotonergic stimulants like methamphetamine and MDMA.
 
nuke said:
I don't think there are a lot of really truly selective 5HT2B antagonists, most of them are also 5HT2A/C antagonists too. The only super selective one is RS-127,445, which was used in the MDMA paper above, but the safety of that falls under who-knows-what. The 5HT2B receptor is targeted by pretty much all psychedelics too, so it may contribute to some of the psychological effects of the drug as well. I don't know if there's been any studies in humans testing this.

The best thing to do is just to avoid serotonergic stimulants like methamphetamine and MDMA.
Click to expand...

agreed
 
fastandbulbous said:
BTW plain ol' dexamphetamine has minimal serotonogic actions, so if you want a stimulant, stick with that and avoid methamphetamine etc
Click to expand...

The toxicity that the OP is asking about arises from peripheral serotonergic activity, not central. Valvular dysfunction, dilated cariomyopathy, and pulmoary hypertension have nothing to do with effects in the CNS.

Does anyone know if the rule "central = peripheral 5HT activity" holds true? I know that methamphetamine causes the above and I didn't think it was that potent of a serotonergic agent
 
Well, it should be possible for a potent, selective 5-HT2b antagonist to be taken concomitantly with MD-x, MD-xx, or a benzofuran to lessen its impact.

RS-127445 might even be an option. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1566110/

It also might be possible to ensure that it doesn't cross the blood brain barrier. Of course, depending on its effects profile, that may not be necessary.

As to 5-HT2b binding's necessity for MD-xx's activity, that's still up for debate. Just look at MDAI.
 
raybeez said:
The toxicity that the OP is asking about arises from peripheral serotonergic activity, not central. Valvular dysfunction, dilated cariomyopathy, and pulmoary hypertension have nothing to do with effects in the CNS.

Does anyone know if the rule "central = peripheral 5HT activity" holds true? I know that methamphetamine causes the above and I didn't think it was that potent of a serotonergic agent
Click to expand...

Methamphetamine is a potent 5-HT releaser, less so than MDMA though.
 
endotropic said:
Methamphetamine is a potent 5-HT releaser, less so than MDMA though.
Click to expand...

Depends on how you use the term "potent".

Methamphetamine is about 10x less potent at 5-HT release than MDMA, and MDMA already requires 100mg for major sero effects.
So that would be 1000mg of methamphetamine for the same sero release.

I wouldn't call a compund that requires a dose of 1000mg potent.
 
I questioned the same thing in regard to aminorex derivates like 4-MAR or 4,4´-DMAR some time ago and searched for a suitable compound but found just the same experimental ones from wikipedia.

It certainly would be nice to have a safe, peripheral-only one available from some RC supply.. when dosed correctly, this could turn the aminorex´es into quite useable drugs.

--

OT, I experienced intense chest pain from combining low-medium dosed DXM (100-150mg/d) with methylphenidate (18mg/d) after a few weeks. I went to the doc but EKG etc. were neutral so he suggested the pain coming from the stomach … Of course I stopped the combo then, but even two years after when taking more than maybe 75mg of DXM the pain reappeared. After researching I found the 5-HT2B and heart valve connection, fearing permanent damage done. Luckily today I can take stimulants again with no chest pain, but is there an easy way to have this checked by a doc?

It may sound silly to take DXM daily but for me it was and is the most effective antidepressant available. Don´t know if this is related to previous unsuccessful and prolonged SSRI therapy tryouts, but taking methylphenidate (or amphetamine) alone usually began to feel very cold and mechanic emotion-wise after a few days on it.
 
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