The interaction of clozapine with the meta-chlorophenylpiperazine (mCPP) discriminative stimulus.
The psychotropic effects of the 5-HT2C agonist mCPP in human subjects are blocked by the atypical antipsychotic clozapine, but not by typical antipsychotics. An understanding of the mechanistic basis for the interaction of clozapine and mCPP would provide further insight into the basis for its unique therapeutic effects in humans. Drug-induced stimulus control provides an animal model for the subjective effects of psychotropic agents in humans. In the present study, the interaction of the atypical antipsychotic clozapine and the typical antipsychotic fluphenazine with the mCPP-stimulus were defined. Neither drug antagonized the stimulus effects of mCPP in vivo. In contrast, clozapine fully antagonized the mCPP-stimulated phosphoinositide turnover at the 5-HT2C receptor in vitro. The present data indicate that the paradigm of mCPP-induced stimulus control does not facilitate the differentiation of atypical and typical antipsychotic activities.
Fiorella
D
D
Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, State University of New York at Buffalo 14214-3000, USA.
Rabin
R A
RA
Winter
J C
JC
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D003024:Clozapine / Q000494:pharmacology*; D004192:Discrimination, Psychological / Q000187:drug effects*; D004347:Drug Interactions; D005476:Fluphenazine / Q000008:administration & dosage / Q000494:pharmacology; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin / Q000187:drug effects
D014150:Antipsychotic Agents; D010879:Piperazines; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin; D003024:Clozapine; C015068:1-(3-chlorophenyl)piperazine; D005476:Fluphenazine