• DOI:10.1111/j.2042-7158.1982.tb04701.x
• Corpus ID: 44968564

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}
}

• M. Fong, S. Garattini, S. Caccia
• Published 1 October 1982
• Chemistry, Psychology, Biology
• Journal of Pharmacy and Pharmacology

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) (Melzacka et al 1980; Cervo et a1 1981) a metabolite resulting from hydrolysis and oxidation in the side-chain of trazodone (Melzacka et a1 1979; Caccia et al 1981a,b). This metabolite acts as a direct 5-HT receptor agonist (Samanin et al 1979; Fuller et al 1980; RokoszPelc et al 1980; Invernizzi et al 1981) and after oral trazodone it accumulates in the rat brain at concentrations comparable to those found after pharmacologically and biochemically effective doses of mCPP (Caccia et al1981b; Cervo et all981). These data, together with the fact that in volunteers given trazodone the metabolite reaches measurable plasma concentrations (Caccia et a1 1982), suggest that mCPP contributes to, or even accounts for, the antidepressant action of the parent drug. Recently, other compounds containing a chlorosubstituted phenylpiperazine have been introduced in psychopharmacology. Examples are etoperidone and mepiprazole (see Fig. 1 for chemical structures) which so far have not been studied from the metabolic point of view. Etoperidone, a triazoloderivative, resembles trazodone in its chemical structure and pharmacological profile (Lisciani et a1 1978; Ramacci et al 1979), while QN’LMR