1‐m‐Chlorophenylpiperazine is an active metabolite common to the psychotropic drugs trazodone, etoperidone and mepiprazole

@article{Fong19821mChlorophenylpiperazineIA,
  title={1‐m‐Chlorophenylpiperazine is an active metabolite common to the psychotropic drugs trazodone, etoperidone and mepiprazole},
  author={M. H. Fong and Silvio Ken Garattini and Silvio Caccia},
  journal={Journal of Pharmacy and Pharmacology},
  year={1982},
  volume={34}
}
In the course of studies on the mechanism of action of trazodone, an antidepressant agent recently introduced into clinical practice (Silvestrini et al 1968; Silvestrini & Lisciani 1973; Brogden et al 1981), it was found that in rats the drug produced the pharmacological effects of a 5-hydroxytryptamine antagonist at low doses but of an agonist at higher doses (Maj et a1 1979). Subsequent studies revealed that the latter effect was due to the formation of 1-m-chlorophenylpiperazine (mCPP… 
Etoperidone, trazodone and MCPP: in vitro and in vivo identification of serotonin 5-HT1A (antagonistic) activity
TLDR
A predominant antagonistic activity of etoperidone, trazodone and MCPP at 5-HT1A receptor sites in rat central nervous system is suggested and one cannot rule out the possibility that these compounds are weak partial agonists.
Disposition of the psychotropic drugs buspirone, MJ-13805 and piribedil, and of their common active metabolite 1-(2-pyrimidinyl)-piperazine in the rat.
TLDR
Results indicate that PmP formation is a pharmacologically significant process for both buspirone and MJ-13805 but it is probably less important for piribedil.
Disposition and metabolism of buspirone and its metabolite 1-(2-pyrimidinyl)-piperazine in the rat.
TLDR
The metabolite 1-(2-pyrimidinyl)-piperazine (1-PP) has a longer t1/2 than buspirone and may contribute to the pharmacological effect of the parent drug.
Blockade of conditioned avoidance responding by trazodone, etoperidone, and MCPP
TLDR
The data suggest TZ and ET may block CAR via formation of MCPP, and the serotonin receptor blocker metergoline significantly reduced the CAR block produced by each, suggesting a serotonergic mechanism of action.
Discriminative stimulus properties of mCPP: evidence for a 5-HT2C receptor mode of action
TLDR
The results show that the discriminative stimulus effects of mCPP’s are predominantly mediated by 5-HT2C receptors, and to some extent by 6-chloro-2-(1-piperazinyl)-pyrazine receptors, with an additional role for 5- HT1B receptors.
Detection of Novel Reactive Metabolites of Trazodone: Evidence for CYP2D6-Mediated Bioactivation of m-Chlorophenylpiperazine
TLDR
Several new glutathione adducts (M3–M7) of trazodone were tentatively identified in human liver microsomal incubations using liquid chromatography-tandem mass spectrometry (LC/MS/MS) and the bioactivation mechanism, a regioisomer of m-CPP, 1-(4′-chlorophenyl)piperazine, was incubated in human Liver microsomes, to investigate the bio activation mechanism.
Effect of meta-chlorophenylpiperazine (mCPP), a central serotonin agonist and vascular serotonin receptor antagonist, on blood pressure in SHR.
TLDR
Although mCPP could be demonstrated to activate central serotonergic receptors and block peripheral vascular 5HT2 receptors, it produced little effect on blood pressure in either the anesthetized or conscious spontaneously hypertensive rat (SHR) up to 1 hr after intraperitoneal administration, consistent with initial studies in normotensive humans.
Pharmacokinetics of trazodone and its major metabolite m-chlorophenylpiperazine in plasma and brain of rats.
TLDR
Maternally administered trazodone, like many other antidepressants, is distributed to fetal tissues in rodents, reaffirming the need for caution in treating pregnant women with psychoactive drugs.
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References

SHOWING 1-10 OF 13 REFERENCES
Plasma concentrations of trazodone and 1‐(3‐chlorophenyl)piperazine in man after a single oral dose of trazodone
TLDR
Findings suggest that l(3chloropheny1)piperazine contributes to some extent to the therapeutic effect of trazodone in depressed patients.
5‐Hydroxytryptamine‐like properties of m‐chlorophenylpiperazine: comparison with quipazine
TLDR
This study has compared the action of CPP with that of quipazine in respect of their influence on the in vivo activities of tyrosine and tryptophan hydroxylases in male Wistar rats and found that CPP induced a behavioural syndrome characteristic for central 5-HTergic stimulation.
l‐(m‐Chlorophenyl)piperazine: a metabolite of trazodone isolated from rat urine
TLDR
Investigation showed that OTPA, the trazodone metabolite formerly described, was inactive whereas the hypothetical metabolite CPP, not detected so far, induced 5-HT-ergic stimulation similar to that evoked by high doses of traZodone, but obserked immediately after an intravenous injection of CPP.
(—)‐m‐Chlorophenyl‐piperazine, a central 5‐hydroxytryptamine agonist, is a metabolite of trazodone
binding sites, particularly on a brain regional basis, and Fillion, G., Rousselle, J.-C., Fillion, M.-P., Beaudoin, may confirm the existence of separate S-HT receptors. D. M., Goiny, M. R., Deniau.
Blockade by trazodone of naloxone‐precipitated jumping in morphine‐dependent rats: correlation with brain levels of m‐chlorophenylpiperazine
TLDR
The Mechanism of Action of Benzodiazepines, Raven Press, Saner, A., Pletscher, A.
Pharmacological properties of AF 1161, a new psychotropic drug.
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