Behavioural and biochemical evidence of the interaction of the putative antipsychotic agent, BMY 14802 with the 5-HT1A receptor

Eur J Pharmacol. 1991 Oct 29;204(1):21-8. doi: 10.1016/0014-2999(91)90830-j.

Abstract

The behavioural and biochemical profile of the sigma ligand and putative antipsychotic agent, BMY 14802 (alpha-(4-fluorophenyl)-4-(5-fluoro-2- pyrimidinyl)-1-piperazine butanol) has been determined in the mouse and rat. In mice, pretreatment with BMY 14802 attenuated both amphetamine-induced hyperactivity and conditioned avoidance responding, consistent with its previously reported antipsychotic potential. In common with 5-HT1A receptor agonists or partial agonists, BMY 14802 induced (a) a dose-dependent hypothermia in mice; (b) aspects of the 5-HT behavioural syndrome in rats, (c) antagonised mescaline-induced head twitches in mice and (d) generalised to the 8-hydroxy-2-(di-n-propylamino)tetralin discriminative stimulus over the dose range of 3-15 mg/kg. BMY 14802 had appreciable affinity for the 5-HT1A receptor (pIC50 = 6.7 compared to 7.3 for sigma binding) and antagonised forskolin-stimulated adenylate cyclase activity with a pEC50 of 6.2, consistent with an agonist action at this receptor. The results support the involvement of 5-HT1A receptors, but not the sigma binding site, in the behavioural profile of BMY 14802.

MeSH terms

  • 8-Hydroxy-2-(di-n-propylamino)tetralin
  • Amphetamine / pharmacology
  • Animals
  • Avoidance Learning / drug effects
  • Behavior, Animal / drug effects*
  • Body Temperature / drug effects
  • Discrimination Learning / drug effects
  • Drug Interactions
  • Hyperkinesis / chemically induced
  • Hyperkinesis / drug therapy
  • Male
  • Mice
  • Pyrimidines / metabolism
  • Pyrimidines / pharmacology*
  • Radioligand Assay
  • Rats
  • Rats, Inbred Strains
  • Receptors, Serotonin / drug effects*
  • Receptors, Serotonin / metabolism
  • Rectum / drug effects
  • Rectum / physiology
  • Tetrahydronaphthalenes / pharmacology
  • Tranquilizing Agents / metabolism
  • Tranquilizing Agents / pharmacology*

Substances

  • Pyrimidines
  • Receptors, Serotonin
  • Tetrahydronaphthalenes
  • Tranquilizing Agents
  • alpha-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazine butanol
  • 8-Hydroxy-2-(di-n-propylamino)tetralin
  • Amphetamine