Further evidence for clozapine as a dopamine D1 receptor agonist

Eur J Pharmacol. 1996 Jun 20;307(1):27-31. doi: 10.1016/0014-2999(96)00181-1.

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 D1 receptor antagonist (+)-5-(2,3-dihydrobenzofuran-7-yl)-3-methyl-8-nitro-2,3,4, 5-tetrahydro-1 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 D1 receptor agonist properties of clozapine.

MeSH terms

  • Animals
  • Benzazepines / pharmacology
  • Benzofurans / pharmacology
  • Body Temperature / drug effects
  • Clozapine / analogs & derivatives
  • Clozapine / pharmacology*
  • Dopamine Agonists / pharmacology*
  • Dopamine Antagonists / pharmacology
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Dopamine D2 / agonists*
  • Sensitivity and Specificity

Substances

  • Benzazepines
  • Benzofurans
  • Dopamine Agonists
  • Dopamine Antagonists
  • Receptors, Dopamine D2
  • 5-(2,3-dihydrobenzofuran-7-yl)-3-methyl-8-nitro-2,3,4,5-tetrahydro-1H-3-benzazepin-7-ol
  • norclozapine
  • Clozapine
  • clozapine N-oxide