FURTHER EVIDENCE FOR CLOZAPINE AS A DOPAMINE D-1 RECEPTOR AGONIST

Clozapine (0.625-10.0 mg kg(-1) s.c.), but not the two major clozapine metabolites, N-desmethylclozapine (0.625-10.0 mg kg(-1) s.c.) or cloz apine-N-oxide (0.625-10.0 mg kg(-1) s.c.), caused a dose-dependent dec rease in core temperature in the rat. Furthermore, the clozapine-induc ed hypothermia (2.5 mgr kg(-1), s.c.) was fully antagonised by pretrea tment with the selective dopamine D-1 receptor -8-nitro-2,3,4,5-tetrah ydro-1H-3-benzazepine-7-ol, maleate (MNC 687) (4.0 mg kg(-1) s.c.). NN C 687 by itself (2.0-8.0 mg kg(-1) s.c.) did not affect core temperatu re. The present results provide further evidence for the dopamine D-1 receptor agonist properties of clozapine.