Clozapine pre-treatment enhances raclopride catalepsy

Eur J Pharmacol. 1999 Jul 14;377(1):R1-2. doi: 10.1016/s0014-2999(99)00406-9.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antipsychotic Agents / pharmacology*
  • Catalepsy / chemically induced
  • Catalepsy / pathology*
  • Clozapine / pharmacology*
  • Drug Synergism
  • Raclopride
  • Rats
  • Rats, Sprague-Dawley
  • Salicylamides / pharmacology*
  • Severity of Illness Index

Substances

  • Antipsychotic Agents
  • Salicylamides
  • Raclopride
  • Clozapine