Is there a way to block the toxicity caused by 5HTP2b agonism?

[Druidus]

This is perhaps not the correct place to ask this question, though I feel I am most likely to get correct info on the subject here. Please, if it should be elsewhere then correct my error and move it for me
. Excuse my brevity, I am forced to post from a phone at the moment. Thanks in advance for any and all of the help and discussion to follow, I truly do appreciate it.

Now my question: Is it theoretically possible to protect against or block the negative affects (notably in the heart and eyes) of 5HT2b agonsim caused by many seratonergic psychoactive chemicals? Would using a long-lasting 5HTP2b selective antagonist before taking the chemical that causes 5HTP2b agonism help, or have any effect? Perhaps something like SB-204741, which is a highly specific
antagonist of 5-HT2B that has negligible effects on 5-HT2A or 5-HT2C?

I'm very curious if this specific kind of toxicity can be blocked somehow. Thanks again, BLers, for your help.

 

[t_wrex]

I'm not certain, but I would think that blocking the 5HT2B action would result in diminished, or nonexistent, trip. It's already known that antipsychotics, some of which are serotonin antagonists, reduce or block trip effects.

I think how the 5HT2B receptor gets agonized makes a difference on toxicity; activation caused by the release of neurotransmitters appears to be more toxic than activation by binding of the psychedelic molecule.

Also, do you happen to have any source citations for toxicity on heart or eyes? Would be interested to read them.

 

[sekio]

Most drugs that act as 5HT2b agonists are not acutely toxic. To my recollection the issue is from chronic, regular dosing causing cardiac valve problems. (c.f. the Fen-Phen crisis)

Among others LSD, DMT, MDMA, psilocin, etc. are all 5-HT2b agonists. Also drugs like oxymetazoline (used in OTC nasal decongestant sprays)... if it were toxic then we would have known it by now.

 

[Druidus]

Thanks, both of you, for the replies.

I'm asking partly due to an interest in chemicals like 6-APB and 5-MAPB, as well as similar drugs (but also just generally. I'm not sure which of those does it, but I think one of them binds to 5-HT2b with something like a 1000 times more selectivity for 5-HT2b than MDMA, which just seems kind of concerning to me.

I suppose it would definitely influence the trip, though I'm not sure how, exactly.

I will check my folders to find the stuff I've seen regarding the eye and heart toxicity. I'll try to post it tonight, but if not it will be tomorrow.

 

[atara]

Remember that receptor binding assays are not really the most reliable basket of techniques in biochemistry -- I've seen different studies give wildly different binding profiles for the same drugs! I do recall one study which said 6-APB was principally a 5-ht2b agonist, but I wouldn't regard this as confirmed until it's been replicated. Wiki believes it though:

6-APB - Wikipedia

en.wikipedia.org

 

[G_Chem]

In this article...

Role of Serotonin via 5-HT2B Receptors in the Reinforcing Effects of MDMA in Mice

The amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) reverses dopamine and serotonin transporters to produce efflux of dopamine and serotonin, respectively, in regions of the brain that have been implicated in reward. However, the role of serotonin/dopamine interactions...

journals.plos.org

They seem to conclude 5-ht2b has an effect on the reinforcing effects of MDMA.

This article...

5-HT2B receptors are required for serotonin-selective antidepressant actions

The therapeutic effects induced by serotonin-selective reuptake inhibitor (SSRI) antidepressants are initially triggered by blocking the serotonin transporter and rely on long-term adaptations of pre- and post-synaptic receptors. We show here that long-term ...

www.ncbi.nlm.nih.gov

Shows an “antidepressant” (euphoria?) effect with it.


After comparing MDMA to 5-MAPB and other APB’s I believe it’s the agonism of this receptor that allows these drugs the extra something that gives burnt out MDMA users a feeling like they never lost the magic to begin with.

To block this would mean to block the positive effects of the drug.

-GC