title: Clozapine pre-treatment enhances raclopride catalepsy.
abstract: The clinical replacement of clozapine by another antipsychotic sometimes causes extrapyramidal signs, including dystonia, to appear suddenly. The present study was done, therefore, to test whether clozapine pre-treatment of rats could affect raclopride-induced catalepsy. Clozapine, at 5 mg/kg, given 2 h before a catalepsy-threshold dose of 0.1 mg/kg raclopride, markedly enhanced raclopride-induced catalepsy in the rats. The results are compatible with earlier in vitro data where pre-exposure of human cloned dopamine D2 receptors to clozapine resulted in an increased potency of raclopride in inhibiting the binding of [3H]clozapine to the receptors. The mechanism of clozapine potentiation of raclopride action may contribute to the clinically observed post-clozapine dystonia.
authors.affiliation: Department of Psychiatry, University of Toronto, Canada.
authors.forename: M L
authors.initials: ML
authors.lastname: Wadenberg
authors.forename: P
authors.initials: P
authors.lastname: Seeman
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D002375:Catalepsy / Q000139:chemically induced / Q000473:pathology*; D003024:Clozapine / Q000494:pharmacology*; D004357:Drug Synergism; D020891:Raclopride; D051381:Rats; D017207:Rats, Sprague-Dawley; D012457:Salicylamides / Q000494:pharmacology*; D012720:Severity of Illness Index
chemical_list: D014150:Antipsychotic Agents; D012457:Salicylamides; D020891:Raclopride; D003024:Clozapine