What exactly does M-cpp do in the brain?

[Don Luigi]

As many are aware, there were/still are alot of M-cpp pills being sold as ecstasy recently. I found these pills to be a not so pleasant experience. But after searching the internet I was unable to find out what receptors M-cpp affects.

MDMA mainly affects serotonin receptors but can anyone please tell me what receptors M-cpp affects? I ask this because I am curious to know wether MDMA would give lesser effects if someone had been taking the M-cpp pills ie. If it releases serotonin. Thanks

 

[fastandbulbous]

I believe it's active at the 5HT2c receptor (& possibly others). It's a metabolite of one of the newer antidepressants as well. The thing that gets me though is that I've seen it referred to as a 'panicogen' (it's as the name suggests - a producer of panic states) in more than one research article and that sounds about as far from MDMA as you can get...

 

[Don Luigi]

Yes it does sound as far from MDMA as you can get, it's basically the opposite(well except for a few exceptions from some peoples experiences). Are the newer antidepressants your talking about SRNI's?

I read somewhere that M-cpp was a research chemical that they were planning on using to help recovering alcoholics to mimic the effects of alcohol. I tried the M-cpp sharks three times (Its stupid but I wanted to 'beat' the drug and have a good experience from it. The third time was alright because I was alone). Panicogen seems to sum it up perfectly or anxiogen because I was laying curled in a ball with my eyes closed and hands over my ears, everything I heard felt like it was coming at me very fast although alot of nice things appeared in my 'minds eye'.

But it did not appear to affect my experience with MDMA a week later.

 

[Dr.Heckyll]

It's a metabolite of the antidepressant trazodone.

 

[Beenhead]

Brand name Deseryl right?

 

[djfriendly]

An individual on a different board put together this assortment of piperazine information:


Pharmacokinetic and pharmacodynamic profile of oral and intravenous meta-chlorophenylpiperazine in healthy volunteers.

Gijsman HJ, Van Gerven JM, Tieleman MC, Schoemaker RC, Pieters MS, Ferrari MD, Cohen AF, Van Kempen GM.

Department of Psychiatry, Centre for Human Drug Research, Leiden University Medical Centre, The Netherlands.

meta-Chlorophenylpiperazine (mCPP) is a compound that is frequently used in challenge tests of the serotonergic system. Its human pharmacology is largely unexplored. The objective of this study was to investigate the pharmacokinetic and pharmacodynamic profile of mCPP. Eight female and six male healthy volunteers were included in a randomized, double-blind, double-dummy, three-way crossover design of single-dose intravenous (0.1 mg/kg), oral (0.5 mg/kg), and placebo treatment, with 24-hour follow-up. mCPP showed a large variability in clearance (11-92 mL/hr) and bioavailability (14-108%). Two female subjects dropped out because of headache and dysphoria. During the 27 occasions in which mCPP was administered, autonomic physical symptoms were observed in 23 subjects and disturbances of mood in 6 subjects. Oral and intravenous mCPP caused sudden increases in cortisol levels, prolactin levels, and total scores of the Body Sensation Questionnaire. Administration of mCPP also led to concentration-dependent increases of saccadic peak velocity and adaptive tracking performance and to a decrease of electroencephalographic occipital theta activity. No clinically relevant effects on electrocardiogram, temperature, and blood pressure were found. In conclusion, it is doubtful whether mCPP is a useful compound for challenge tests in view of the large pharmacokinetic variability after intravenous and oral administration. The effects of mCPP are consistent with disinhibition of the central nervous system.


Psychopharmacology (Berl). 1990;100(3):339-44. Links
Effects of m-chlorophenylpiperazine in normal subjects: a dose-response study.Kahn RS, Wetzler S, Asnis GM, Kling MA, Suckow RF, van Praag HM.
Department of Psychiatry, Albert Einstein College of Medicine, Montefiore Medical Center, New York, NY 10467.

m-Chlorophenylpiperazine (MCPP), a direct 5HT receptor agonist, was administered orally to 20 normal subjects in two doses (0.25 and 0.5 mg/kg) in a placebo-controlled design. Behavioral responses; ACTH, cortisol, prolactin and MCPP blood level; temperature and pulse rate were measured over a 210-min period after administration of tablets. Non-linear dose-response relationships between MCPP and ACTH, cortisol and prolactin response were found. On the higher dose, a significant increase in the number of physical symptoms was also noted and three subjects (15%) had a panic attack, while one subject (5%) had a panic attack on the lower dose. No effects on other behavioral variables, pulse rate and temperature were found using either dose. These findings attest to the usefulness of MCPP as a challenge agent to assess 5HT receptor hypersensitivity when given at a low oral dose (i.e. around 0.25 mg/kg), and to assess 5HT receptor hyposensitivity when given at higher oral doses (i.e. around 0.5 mg/kg).

 

[djfriendly]

Apparently I need to split this into shorter posts:



Psychiatry Res. 1990 Aug;33(2):189-98. Links
Effects of serotonin antagonists on m-chlorophenylpiperazine-mediated responses in normal subjects.Kahn RS, Kalus O, Wetzler S, Cahn W, Asnis GM, van Praag HM.
Department of Psychiatry, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY.

The serotonin (5HT) agonist, m-chlorophenylpiperazine (MCPP), has been used as a challenge agent to assess central 5HT receptor sensitivity in normal subjects and patients with panic disorder, obsessive-compulsive disorder, and major depression. Adrenocorticotropin, cortisol, and prolactin responses to MCPP were among the variables measured. MCPP's usefulness as a probe of 5HT receptors, however, hinges on its 5HT selectivity. To address MCPP's selectivity for 5HT, this study tested whether two different 5HT antagonists, methysergide (4 mg p.o.) and metergoline (4 mg p.o.), could block the hormonal and behavioral effects of MCPP (0.5 mg/kg p.o.) in 10 normal male subjects in comparison to placebo. Both 5HT antagonists abolished the prolactin release to MCPP. Metergoline, the antagonist with the more potent 5HT binding affinity, significantly blocked MCPP's effect on cortisol release as compared to placebo, and methysergide showed a nonsignificant trend to that effect. MCPP alone did not have a significant effect on behavioral variables, perhaps explaining why neither 5HT antagonist affected these measures. The findings from this study suggest that both MCPP-induced prolactin release and cortisol release are indeed 5HT-mediated effects.

Psychopharmacology (Berl). 1992;106(3):388-90. Links
A dose-response study of intravenous m-chlorophenylpiperazine in normal subjects.Kalus O, Wetzler S, Kahn RS, Asnis GM, van Praag HM.
Department of Psychiatry, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY.

A placebo-controlled dose-response study of the direct serotonin receptor agonist m-chlorophenylpiperazine (MCPP), intravenously infused over 90 s in 0.06 and 0.08 mg/kg doses, was conducted in nine normal male subjects. Cortisol, prolactin, MCPP serum levels and behavioral responses were measured over a 210-min period. Both doses caused significant cortisol and prolactin release and were associated with significantly greater behavioral effects as compared to placebo. Though the two doses were associated with different MCPP serum levels, they did not significantly differ in their hormonal and behavioral effects.


The application of the principles of clinical drug development to pharmacological challenge tests of the serotonergic system.

J Psychopharmacol. 2004 Mar;18(1):7-13.

Gijsman HJ, Cohen AF, van Gerven JM.
South London and Maudsley NHS Trust, London, UK. [email protected]

 

[djfriendly]

That's only a sampling, but I'll leave it at that to avoid cluttering the thread.

Instead, I've saved it all as a word document, which is attached to this post.

 

[Don Luigi]

thanks

 

[BilZ0r]

Nice work djfriendly.

 

[djfriendly]

Thanks, but as I noted, all I did was copy-n-paste it, I don't want to take credit for all the work someone else did!

 

[Helios.]

mCPP (meta-chlorophenylpiperazine) tranquilizes the brain. I wouldn't call it a panicogen, but it is a bit dissociative and a tad trippy.

 

[Jamshyd]

It's a metabolite of the antidepressant trazodone.

That is strange. Trazodone was one of the few things that worked for me (at least in terms of immediate efficacy), and I do have rampant panic attacks...

EDIT: As in, I normally have rampant panic attacks, and Trazodone seemed to be efficiently anxiolytic.

 

[Helios.]

^I like trazodone, too. In fact, I took 2 of them last night. In high (around 600mg) doses, trazodone is a great erection stimulator for men.

 

[Matt the Raver]

Okey Dokey......I'll try and straighten all this our as best I can.....
I was doing a PhD on the effects of the stress hormone glucocorticoid on 5HT2C, so I've done a fair bit of reading on this.......
The serotonin2C receptor predominantly couples to Gq and promotes PKC activity and intracellular Ca2+ release.
It's expressed in GABAergic neurones in the Substania Nigra and Ventral Tegmental Area.
These GABAergic neurones synapse with Dopaminergic neurones, inhibiting DA release. So more 5HT2C activity=less DA release.
Secondly, 5HT2C is expressed on Glutamatergic neurones in a region called the Basolateral amygdala (BLA), which is important for learning fear responses. Basically BLA activity doesn't feel very nice and a 5HT2C agonist just happens to increase it.
It also promotes glucorticoid release, which is not very nice either, but hormones were never really my thing.....
So.......to review switching on 5HT2C reduces DA release and increases BLA activity.
As methyl chloro phenyl piperazine (mCPP) is a 5HT2A/C agonist, baring all this in mind you'ld get a drug which is trippy, a bit sedating and probably kinda scary as well.

 

[Matt the Raver]

Oh.....and trazodone is supposedly a 5HT2 antagonist (according to wikipedia).
This would mean it increases DA release (by blocking 2C) and stops fuzziness (by blocking 2A).
The fact that a metabolite has the opposite effect seems kinda fucked up (but 2C agonists do cause boners for some strange reason).

 

[Matt the Raver]

5HT2C is very important in the action of serotonin releasing agents, mainly because it plays a key role in regulating DA.
It's spontaneously active, but shows a reduced level of activity on being exposed to agonists until it becomes desensitised, resulting in increased DA release.

 

[Jamshyd]

Secondly, 5HT2C is expressed on Glutamatergic neurones in a region called the Basolateral amygdala (BLA), which is important for learning fear responses. Basically BLA activity doesn't feel very nice and a 5HT2C agonist just happens to increase it.

Yet more evidence for my (well, at least I was the first to mention it on this board ) idea that antagonising glutamate in the amygdala is a superior cure for depression and anxiety .

 

[nuke]

Doesn't MK-801 antagonize glutamate there? And the universal consensus for that compound is dysphoria..

 

[Matt the Raver]

Amygdaloid activity is very important in the anxiety seen in depressive behaviour. (I read a really good paper on behavioural work done on rats using a 5HT2C agonst, which I'll dig it out later).
That said, a review of amygdaloid neurobiology is beyond the scope of this thread (If the interest's there I'll do one).
As for MK-801, to my understanding it's an NMDA antagonist (just like PCP or ketamine). But as NMDA is expressed VERY widely throughout the brain. It means its effects are equally ubiquitous.
I'ld expect an NMDA antagonist to inhibit the learning of fear responses, but it'ld also inhibit hippocampal activity (see neurogenic theory of depression) and alot of cortical activity as well.

I'm intrigued that different NMDA antagonists seem to have differing behavioural effects, but again I think this is a bit beyond the scope of a thread on mCPP!