title: In vivo comparison of two 5-HT1A receptors agonists alnespirone (S-20499) and buspirone on locus coeruleus neuronal activity.
abstract: The aim of the present study was to compare, in chloral-hydrate anaesthetized rats, the alpha(2)-adrenergic properties of the selective 5-HT(1A) receptor agonist, alnespirone (S-20499), with those of buspirone, a 5-HT(1A) receptor agonist exhibiting potent alpha(2)-adrenoceptor antagonist properties via its principal metabolite, 1-(2-pyrimidinyl)-piperazine. Both locus coeruleus spontaneous firing activity and noradrenaline release in the medial prefrontal cortex were potently inhibited by the alpha(2)-adrenoceptor agonist clonidine, at a dose of 40 microg/kg (i.p.). Such an inhibition was neither prevented nor reversed by alnespirone (10 mg/kg, i.p.), while buspirone, at the same dose, potently antagonized the locus coeruleus inhibitory effects of clonidine. These data demonstrate that, in contrast with some aryl-piperazine compounds (such as buspirone), alnespirone, either on its own or via a possible metabolite such as buspirone, is devoid in vivo of significant alpha(2)-adrenoceptor antagonist properties.
authors.affiliation: Laboratoire de Neuropharmacologie et de Neurochimie, INSERM Unité 512, Faculté de Pharmacie, Université Claude Bernard Lyon 1, 8, Avenue Rockefeller, 69373 Cedex 08, Lyon, France. astier@rockefeller.univ-lyon1.fr
authors.forename: Bernadette
authors.initials: B
authors.lastname: Astier
authors.forename: Laura
authors.initials: L
authors.lastname: Lambás Señas
authors.forename: Fabienne
authors.initials: F
authors.lastname: Soulière
authors.forename: Patricia
authors.initials: P
authors.lastname: Schmitt
authors.forename: Nadia
authors.initials: N
authors.lastname: Urbain
authors.forename: Nicolas
authors.initials: N
authors.lastname: Rentero
authors.forename: Lionel
authors.initials: L
authors.lastname: Bert
authors.forename: Luc
authors.initials: L
authors.lastname: Denoroy
authors.forename: Bernard
authors.initials: B
authors.lastname: Renaud
authors.forename: Monique
authors.initials: M
authors.lastname: Lesourd
authors.forename: Carmen
authors.initials: C
authors.lastname: Muñoz
authors.forename: Guy
authors.initials: G
authors.lastname: Chouvet
mesh_terms: D000818:Animals; D002065:Buspirone / Q000494:pharmacology*; D003000:Clonidine / Q000494:pharmacology; D004594:Electrophysiology; D008125:Locus Coeruleus / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D008297:Male; D017551:Microdialysis; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D009638:Norepinephrine / Q000378:metabolism; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000502:physiology; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013141:Spiro Compounds / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists; D013141:Spiro Compounds; C075319:alnespirone; D003000:Clonidine; D002065:Buspirone; D009638:Norepinephrine