title: Effects of a potential antipsychotic, BMY 14802, on firing of central serotonergic and noradrenergic neurons in rats.
abstract: BMY 14802 (alpha-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1- piperazinebutanol HCl) is a novel potential antipsychotic drug which does not bind to dopamine receptors, does bind to 5-HT1A receptors, and also binds stereoselectively to sigma sites. The effects of acute systemic administration of this compound on spontaneously firing serotonergic dorsal raphe neurons and noradrenergic locus coeruleus neurons were assessed by means of extracellular single unit recordings in chloral hydrate anesthetized male Sprague-Dawley rats. (+/-)-BMY 14802 produced inhibition of firing of serotonergic dorsal raphe neurons when given intravenously (ED50 = 0.19 mg/kg) and intragastrically (effective dose = 20 mg/kg). Racemic and enantiomeric BMY 14802 mainly produced mild increases in firing (approximately 60% or less) of noradrenergic locus coeruleus neurons, with (-)-BMY 14802 slightly more potent (ED25 = 0.31 mg/kg i.v.) than (+)-BMY 14802 (ED25 = 0.55 mg/kg i.v.), and the racemate being intermediate (ED25 = 0.36 mg/kg i.v.). These electrophysiological studies demonstrate that in this rat preparation acute systemic administration of BMY 14802 produces changes in serotonergic and noradrenergic brain function.
authors.affiliation: Bristol-Myers Squibb Company, Pharmaceutical Research and Development Division, Wallingford, CT 06492.
authors.forename: C P
authors.initials: CP
authors.lastname: VanderMaelen
authors.forename: J P
authors.initials: JP
authors.lastname: Braselton
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D014150:Antipsychotic Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D008125:Locus Coeruleus / Q000166:cytology; D008297:Male; D009474:Neurons / Q000187:drug effects*; D009638:Norepinephrine / Q000502:physiology*; D011743:Pyrimidines / Q000494:pharmacology*; D011903:Raphe Nuclei / Q000166:cytology; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000502:physiology*; D013237:Stereoisomerism
chemical_list: D014151:Anti-Anxiety Agents; D014150:Antipsychotic Agents; D011743:Pyrimidines; C050408:alpha-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazine butanol; D012701:Serotonin; D009638:Norepinephrine