do psychedelics interact with the 5-HT3 receptor?

[djfriendly]

I'm considering using a new anti-smoking drug called varenicline (Chantix). This drug primarily interacts with nicotinic receptors, however it also binds to the 5-HT3 receptor "with moderate affinity."

Do psychedelics, or the MDx family drugs, interact with the 5-HT3 receptor? Though I don't trip very often, I'd rather go cold turkey than mess with any receptors which are necessary to enjoy psychedelics.

 

[HeaT]

IT seems that 2-Me-5HT is the only MAJOR agonist, but some benzodiazepines can be antagonists, as can some semi-indole compounds. But honestly, I HIGHLY doubt any negative effects will be noticed, as the 5-HT3 receptor deals mainly with nausea and stuff, so it wouldn't riun your trip. Sorry I didn't help much, but you can always start small and work your way up. Your body has a mildly large margin of error, if you fuck up, it will fix itself, so you can ingest a small amount and "fuck up" safely, generally.

 

[fastandbulbous]

I'm considering using a new anti-smoking drug called varenicline (Chantix). This drug primarily interacts with nicotinic receptors, however it also binds to the 5-HT3 receptor "with moderate affinity."

Do psychedelics, or the MDx family drugs, interact with the 5-HT3 receptor? Though I don't trip very often, I'd rather go cold turkey than mess with any receptors which are necessary to enjoy psychedelics.

Nicotinic receptors and 5HT-3 receptors - I'd make sure you have a sick-bag with you at all times as the dopamine released through nicotinic receptor stimulation combined with the 5HT3 receptors in the gut sounds like a recipie for a pukefest!

 

[5-HT2]

[memberate]move to ADD perhaps?[/memberate]

 

[Xorkoth]

I'll take your suggestion, since this really does deal more with neurochemistry than psychedelics. It's moved.

 

[djfriendly]

Nicotinic receptors and 5HT-3 receptors - I'd make sure you have a sick-bag with you at all times as the dopamine released through nicotinic receptor stimulation combined with the 5HT3 receptors in the gut sounds like a recipie for a pukefest!

It seems to be the only common negative effect, reported by 16-40% of subjects in studies. I'm hoping to be one of the lucky 60-84%. This drug kicked bupropion's ass at quit rates in the studies.

Hell, 16-40% seems to roughly correspond to the incidence of nausea reported from some drugs commonly discussed in PD.

 

[Dondante]

I remember ibogaine having some degree of affinity, but I don't remember if it was significant. 5HT3 is interesting in that it's the only non G-protein mediated receptor in the serotonin family. It's a voltage gated ion channel.

But no, most psychs don't interact with it.

 

[Matt the Raver]

I've just had a quick browse through this:

https://rikki.fi/tajkor/bl/A review of central 5-HT receptors and their function.pdf

(I couldn't open it in internet explorer, but I could with firefox)

It says that 5HT3 activation increases DA release and increases aversive behaviour (which seems odd).

5HT3 agonists also disrupt LTP in the hippocampus, but unlike 5HT2A, 5HT3 isn't expressed highly in cortex which means any trippy effects are unlikely.

5HT3 agonist do cause nausea though and since ethanol bind allosterically to 5HT3 (and possibly to other ligand gated ion channels, such as GABAa and nACh).

Which might explain in part, why getting drunk makes you sedated, disrupts your memory and makes you hurl.

MDx drugs will presumably affect 5HT3 receptors as 5HT levels increase. But then there are (at least) 13 other 5HT receptors which would get activated as well, so trying to attribute specific effects any given receptor requires something a bit more selective.

 

[Psychedelics_r_best]

Wait guys, I have a retard question to ask for you guys. What are the receptors that dopamine and norepinephrine bind to? What receptors do exogenous amphetamines such as amphetamine and methamphetamine bind to?

I know there is a general difference between the affinity tryptamine and phenethylamine/ amphetamine psychedelics have to certain serotonin receptors. What are they again? I believe tryptamines have an affinity for 5-HT2a in general and phenethylamines more so for 5-HT2c.

 

[djfriendly]

This is a simple question so I'll give a shot and hope I get this correct. Dopamine binds to dopamine receptors. Clever, eh? Norepinephren binds to adrenergic receptors. Both are the same receptors with which amphetamine will interact I think, plus possibly some others.

 

[Psychedelics_r_best]

Youre pretty clever. Norepinephrine and dopamine are quite similar however, I would think a single class of receptors mediated the signals that both induce.

Disregard me though, I'm not well versed at all. I just meant to say that I guess this receptors must be very specific if they are to differentiate between adrenaline and norepinephrine.

 

[almost-]

Intrathecal 5-methoxy-N,N-dimethyltryptamine in mice modulates 5-HT1 and 5-HT3 receptors.
Alhaider AA, Hamon M, Wilcox GL.
Eur J Pharmacol. 1993 Nov 9;249(2):151-60.

The antinociceptive effects of intrathecally administered 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), a potent 5-HT receptor agonist, were studied in three behavioral tests in mice: the tail-flick test and the intrathecal substance P and N-methyl-D-aspartic acid (NMDA) assays. Intrathecal administration of 5-MeO-DMT (4.6-92 nmol/mouse) produced a significant prolongation of the tail-flick latency. This action was blocked by 5-HT3 and gamma-aminobutyric acidA (GABAA) receptor antagonists but not by 5-HT2, 5-HT1A, 5-HT1B or 5-HT1S receptor antagonists. Binding studies indicated that 5-MeO-DMT had very low affinity for 5-HT3 receptors. 5-MeO-DMT inhibited biting behavior while increasing scratching behavior induced by intrathecally administered substance P. The inhibition of biting behavior was antagonized by intrathecal co-administration of 5-HT1B and GABAA receptor antagonists while 5-HT1A, 5-HT1S, 5-HT2 and 5-HT3 receptor antagonists had no effect. 5-MeO-DMT-enhanced scratching behavior was inhibited by all the antagonists used except ketanserin and bicuculline, suggesting the involvement of 5-HT1A, 5-HT1B, 5-HT1S, 5-HT3 and GABAA receptors. NMDA-induced biting behavior was inhibited by 5-MeO-DMT pretreatment; this action was antagonized by 5-HT1B, 5-HT3 and GABAA receptor antagonists. The involvement of these receptors in 5-MeO-DMT action suggests that it may promote release of 5-HT (5-hydroxytryptamine, serotonin).

http://www.ncbi.nlm.nih.gov/entrez/...=Retrieve&dopt=abstractplus&list_uids=7507056

 

[djfriendly]

^ If 5-HT3 is associated with nausea, it's no big surprise that 5-MeO-substituted tryptamines interact with it.

 

[nuke]

Psychedelics with 5HT3 affinities all seem to cause nausea in me, at least for a certain period of time (maybe the reason LSD is so clean-feeling is because it has such low binding affinities for 5HT3).

 

[BilZ0r]

Well amphetamines interact with dopamine, noradrenaline and serotonin transporters, which then release their associated neurotransmitter, and it's the neurotransmitter that interact with the receptors.

But yeah, most psychedelics (pretty much all PEAs) don't hit up 5-HT3 receptors with any affinity worth noting.