Trazodone and MCPP

[AlphaMethylPhenyl]

I have a few questions regarding trazodone:

How much of an effect does MCPP (the what many would say psychedelic [I mean it does agonize most of the 5-HT receptors] metabolite of trazodone) have on trazodone's effect? Is MCPP euphoric? Does it cancel out any of the various antagnistic proflies that trazodone displays on various receptors? Would MCPP be sedating? Is it significantly responsible for its anti-depressant effect? Is it harmful to the heart?

Does trazodone interfere with sleep architecture? Is it in any sense neurotoxic? Is it supposed to be "better" than the benzodiazepine drugs and non-benzodiazepines in treating insomnia, overall?

MCCP is interestingly an antagonist at 5-HT7 http://europepmc.org/abstract/MED/10822046

From wiki: mechansim of MCPP: 5-HT1A, 5-HT1B, 5-HT1D, 5-HT2A, 5-HT2B, 5-HT2C, 5-HT3, and 5-HT7

trazodone mechanism from wiki: 5-HT1A receptor (Kd = 78 nM)
5-HT2A receptor (Ki = 13 nM)
5-HT2B receptor (Ki = 74 nM)[24]
5-HT2C receptor (Ki = 192 nM)
α1-adrenergic receptor (Kd = 39 nM)
α2-adrenergic receptor (Kd = 405 nM)
H1 receptor (Kd = 725 nM)

MCPP (the one I'm most interested in, assuming its largely responsible for trazodones effects):

A bunch of articles I found seem to point to MCPP being anxiogenic (here's one: http://www.sciencedirect.com/science/article/pii/0165178194900019), but that doesn't seem to hold pharmacologically speaking.

http://www.sciencedirect.com/science/article/pii/S0091305798000616 (what is the implication of its effects on the nociceptive response; I thought that nociceptin was the "fourth" opiate sub-type?)

Quite interestingly, though, it seems useful in schizophrenia: http://www.sciencedirect.com/science/article/pii/016517819290136Q. How to explain this?

Useful in SAD: http://www.sciencedirect.com/science/article/pii/0165178194900876

Increased high among alcohol-users, but (further interesting) a decreased need for the drug: http://onlinelibrary.wiley.com/doi/10.1111/j.1530-0277.1997.tb03753.x/abstract

http://www.sciencedirect.com/science/article/pii/0364772280900065 (causes anorexia)

I basically want as much information about trazodone and MCPP as possible.

I might ask more questions later. Thanks.

 

[sekio]

Given that up to ~50% of a dose of trazodone could be converted to mCPP in theory, it's possible that it could play a significant role in the pharmacology of traz. But I seriously doubt all of an absorbed dose of rtazodone is broken down into mCPP.

I do know some people seem to find the "plain" piperazines (not mixed with BZP), in sub-100mg doses, quite pleasant. But of course, some people feel the opposite... mCPP is known to induce migraine pretty reliably in some individuals.

 

[AlphaMethylPhenyl]

Thanks for the quick reply. I did notice a fairly piercing headache (lasting only about five minutes) approximately 24 hours after I took trazodone.

 

[sekio]

That is very unlikely to be caused by trazodone, given that mCPP would be showing up in your blood only a few hours after ingestion.

How much of an effect does MCPP have on trazodone's effect? Is MCPP euphoric? Does it cancel out any of the various antagnistic proflies that trazodone displays on various receptors? Would MCPP be sedating? Is it significantly responsible for its anti-depressant effect? Is it harmful to the heart?

Does trazodone interfere with sleep architecture? Is it in any sense neurotoxic? Is it supposed to be "better" than the benzodiazepine drugs and non-benzodiazepines in treating insomnia, overall?

1. I think it would be personally and dose- dependent. for some the presence of mCPP will make trazodone have an intolerabe side effects profile, for some it won't ever build to significant levels, I would expect....
2. mCPP is considered to be pleasantly euphoric by some, yes.
3. You could check the PDSP database or Ki values; I bet trazodone would outcompete mCPP for most of the serotonin receptors though.
4. mCPP is described as being sedating, or at least not outwardly stimulating, on its own, IIRC
5. It's possible mCPP plays a downstream role in trazodone's effects but AFAIK there haven't been any good studies to suggest that it is, or isn't.
6. I would imagine mCPP would be harmful to the heart and vasculature as a broad spectrum serotonin agonist, but I honestly don't know. As for trazodone, I don't believe so, or it would have a black box warning, I'd think.
7. Probably, in some way - most sedatives with a fairly broad spectrum of action do.
8. Probably not.
9. It's a better option to try before running to the BZDs that can produce dependence and addiction and lose their efficacy!