Further evidence for clozapine as a dopamine D 1 receptor agonist

Abstract

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 clozapine- N-oxide (0.625–10.0 mg kg −1 s.c.), caused a dose-dependent decrease in core temperature in the rat. Furthermore, the clozapine-induced hypothermia (2.5 mg kg −1, s.c.) was fully antagonised by pretreatment with the selective dopamine D 1 receptor antagonist (+)-5-(2,3-dihydrobenzofuran-7-yl)-3-methyl-8-nitro-2,3,4,5-tetrahydro-I H-3-benzazepine-7-ol, maleate (NNC 687) (4.0 mg kg −1 s.c.). NNC 687 by itself (2.0–8.0 mg kg −1 s.c.) did not affect core temperature. The present results provide further evidence for the dopamine D 1, receptor agonist properties of clozapine.