title: 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.affiliation: Merck Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Harlow, Essex, U.K.
authors.forename: L J
authors.initials: LJ
authors.lastname: Bristow
authors.forename: L
authors.initials: L
authors.lastname: Baucutt
authors.forename: L
authors.initials: L
authors.lastname: Thorn
authors.forename: P H
authors.initials: PH
authors.lastname: Hutson
authors.forename: A
authors.initials: A
authors.lastname: Noble
authors.forename: M
authors.initials: M
authors.lastname: Beer
authors.forename: D N
authors.initials: DN
authors.lastname: Middlemiss
authors.forename: M D
authors.initials: MD
authors.lastname: Tricklebank
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects*; D001831:Body Temperature / Q000187:drug effects; D004193:Discrimination Learning / Q000187:drug effects; D004347:Drug Interactions; D006948:Hyperkinesis / Q000139:chemically induced / Q000188:drug therapy; D008297:Male; D051379:Mice; D011743:Pyrimidines / Q000378:metabolism / Q000494:pharmacology*; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D012007:Rectum / Q000187:drug effects / Q000502:physiology; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D014149:Tranquilizing Agents / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D011743:Pyrimidines; D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes; D014149:Tranquilizing Agents; C050408:alpha-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazine butanol; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000661:Amphetamine