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

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.

• Authors: L J Bristow, L Baucutt, L Thorn, P H Hutson, A Noble, M Beer, D N Middlemiss, M D Tricklebank
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 204 Issue 1 Pg. 21-8 (Oct 29 1991) ISSN: 0014-2999 [Print] Netherlands
• PMID: 1839533 (Publication Type: Journal Article)

Chemical References

• 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

Topics

• 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, drug therapy)
• Male
• Mice
• Pyrimidines (metabolism, pharmacology)
• Radioligand Assay
• Rats
• Rats, Inbred Strains
• Receptors, Serotonin (drug effects, metabolism)
• Rectum (drug effects, physiology)
• Tetrahydronaphthalenes (pharmacology)
• Tranquilizing Agents (metabolism, pharmacology)