The selective dopamine D3 receptor antagonists, SB 277011-A and S 33084 block haloperidol-induced catalepsy in rats

Eur J Pharmacol. 2007 Oct 31;572(2-3):171-4. doi: 10.1016/j.ejphar.2007.06.035. Epub 2007 Jun 29.

Abstract

SB 277011-A (trans-N-[4-[2-(6-cyano-1,2,3,4-tetrahydroisoquinolin-2-yl)ethyl]cyclohexyl]-4-quinolinecarboxamide) and S 33084 [(3aR,9bS)-N[4-(8-cyano-1,3a,4,9b-tetrahydro-3H-benzopyrano[3,4-c]pyrrole-2-yl)-butyl](4-phenyl)benzamide] were already shown to lack cataleptogenic actions. Further to that, we report that SB 277011 exerted a dose-dependent dampening on the development of haloperidol-induced catalepsy in the dose-range of 13.5-30 mg/kg p.o. while S 33084, at the dose of 0.625 mg/kg sc. significantly inhibited catalepsy induced by haloperidol; had no effect at 1.25 mg/kg, and further augmented the effect of haloperidol after 2.5 mg/kg. The compounds also produced effective inhibition when administered 2 hours after haloperidol. The results underline that dopamine D3 receptor antagonist action may have therapeutic value in the treatment of schizophrenia.

MeSH terms

  • Animals
  • Benzopyrans / pharmacology*
  • Catalepsy / chemically induced
  • Catalepsy / drug therapy*
  • Haloperidol
  • Male
  • Nitriles / pharmacology*
  • Pyrroles / pharmacology*
  • Rats
  • Rats, Wistar
  • Receptors, Dopamine D3 / antagonists & inhibitors*
  • Tetrahydroisoquinolines / pharmacology*

Substances

  • Benzopyrans
  • Nitriles
  • Pyrroles
  • Receptors, Dopamine D3
  • S 33084
  • SB 277011
  • Tetrahydroisoquinolines
  • Haloperidol