2,3-Dichlorophenylpiperazine

[AlphaMethylPhenyl]

Does anyone know what kind of pharmacalogical profile this one carries?

According to Wikipedia its similar to meta-Chlorophenylpiperazine (mCPP), which is an agonist at most serotonin receptors

 

[sekio]

Probably pretty nasty.

The piperazines are also agonists at the 'wrong' 5ht receptors like 3 and 2c, which cause e.,g. nausea and anxiety.

 

[Solipsis]

2C agonism isn't necessarily that 'wrong' though is it? 2C-B and 2C-C are supposed to rely significantly on that action, unless I am mistaken.
Yeah 5-HT3 is associated with nausea of course.

Anyway I'm sure sekio was just giving examples and there are other pharmacological considerations.

An ex housemate tried mCPP once and felt messy and feverish and messed up. I have samples of numerous piperazines but don't plan on ever actually taking them.

 

[sekio]

mCPP's strongest actions are at the 5-HT2B and 5-HT2C receptors and its discriminative cue is mediated primarily by 5-HT2C.[22][27][28] Its negative effects such as anxiety, headaches, and appetite loss are likely mediated by its actions on the 5-HT2C receptor,[7][18][29]

i think the 2c- compounds are partial agonists, too. The piperazines are fullagonists.

either way, reports of people finding the phenyl piperazines (i.e. not BZP) fun and euphoric are few and far between.

(note: the references refer to the 2c receptor as 5-ht1c, which is an antiquated name)

 

[Solipsis]

Lovely, thnx.

I would expect there to be serotonin or monoamine release with piperazines as well, after all they are used as poor MDMA replacements and not psychedelic replacements.
Or is this only from reuptake inhibition? Not sure.
The latter would make it seem like getting 'high' on piperazines is related to why trazodone works. And IMO no one in their right mind should abuse anti-depressants. Although AMT is an example of an exception to that.

 

[specialspack]

2C agonism isn't necessarily that 'wrong' though is it? 2C-B and 2C-C are supposed to rely significantly on that action, unless I am mistaken.

Are you talking about this paper? http://www.ncbi.nlm.nih.gov/pubmed/17337633

Functional selectivity of hallucinogenic phenethylamine and phenylisopropylamine derivatives at human 5-hydroxytryptamine (5-HT)2A and 5-HT2C receptors.
Moya PR, Berg KA, Gutiérrez-Hernandez MA, Sáez-Briones P, Reyes-Parada M, Cassels BK, Clarke WP.


2,5-Dimethoxy-4-substituted phenylisopropylamines and phenethylamines are 5-hydroxytryptamine (serotonin) (5-HT)(2A/2C) agonists. The former are partial to full agonists, whereas the latter are partial to weak agonists. However, most data come from studies analyzing phospholipase C (PLC)-mediated responses, although additional effectors [e.g., phospholipase A(2) (PLA(2))] are associated with these receptors. We compared two homologous series of phenylisopropylamines and phenethylamines measuring both PLA(2) and PLC responses in Chinese hamster ovary-K1 cells expressing human 5-HT(2A) or 5-HT(2C) receptors. In addition, we assayed both groups of compounds as head shake inducers in rats. At the 5-HT(2C) receptor, most compounds were partial agonists for both pathways. Relative efficacy of some phenylisopropylamines was higher for both responses compared with their phenethylamine counterparts, whereas for others, no differences were found. At the 5-HT(2A) receptor, most compounds behaved as partial agonists, but unlike findings at 5-HT(2C) receptors, all phenylisopropylamines were more efficacious than their phenethylamine counterparts. 2,5-Dimethoxyphenylisopropylamine activated only the PLC pathway at both receptor subtypes, 2,5-dimethoxyphenethylamine was selective for PLC at the 5-HT(2C) receptor, and 2,5-dimethoxy-4-nitrophenethylamine was PLA(2)-specific at the 5-HT(2A) receptor. For both receptors, the rank order of efficacy of compounds differed depending upon which response was measured. The phenylisopropylamines were strong head shake inducers, whereas their phenethylamine congeners were not, in agreement with in vitro results and the involvement of 5-HT(2A) receptors in the head shake response. Our results support the concept of functional selectivity and indicate that subtle changes in ligand structure can result in significant differences in the cellular signaling profile.

All that says, unless I'm reading it wrong, is that the DOx series were more efficacious at 5HT2A than 5HT2C than the 2Cx series - which would be in line with their increased potency.

I don't think that this says that 5HT2C is involved in the psychedelic effect, especially given that the suggestion is that 5HT2A is involved in head-shake and 5HT2C is not, if we agree that head-shake is a very rough indication of psychedelic activity (although I struggle with this idea frankly).

Unless there is other work that shows blocking 5HT2C attenuates the effect of 2Cx drugs?

 

[Solipsis]

I would very much like to find those references but I picked up this information from PD at some point, found it quite convincing for some reason, and now don't even know where to start recovering it.

Hopefully someone else will chime in who has learned the same or who knows where I have been misled. Otherwise there will need to be some digging.

 

[specialspack]

Ok well these papers are about DOI rather than the 2C versions - http://link.springer.com/article/10.1007/s00213-010-1784-0?LI=true

We conclude that the HTR to DOI in mice is strongly modulated by 5-HT2C receptor activity. This novel finding invites reassessment of hallucinogenic mechanisms involving 5-HT2 receptors.

Is about DOI but not 2C-I... 5HT2C knockout mice show reduced head twitch, as to wildtype mice pretreated with a 5HT2C antagonist.

And here http://jpet.aspetjournals.org/content/335/3/728.short

The results of these experiments provide strong evidence that DOI-elicited head-twitch behavior is a 5-HT2A agonist-mediated effect, with subsequent inhibition of head-twitch behavior being driven by competing 5-HT2C agonist activity.

This says that 5HT2C agonism reduces head twitch activity, opposite to the study above - pretreatment with 5HT2A agonist reduced heat twitch, pretreatment with 5HT2A antagonist doesn't affect head twitch except to shift the downward portion of the dose-response curve further to the right.

I can't see any papers on the phenethylamine versions and 5HT2C antagonism/knockout. Wiser heads may be able to chip in, although this is now quite off topic and maybe needs restructuring into a thread on its own?

EDIT there is this thread on the mechanism of 2Cxs - http://www.bluelight.ru/vb/threads/518781-mechanism-of-2C-X-compounds?highlight=5ht2c which I suppose some of this could be merged to?