In vivo comparison of two 5-HT1A receptors agonists alnespirone (S-20499) and buspirone on locus coeruleus neuronal activity.
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.
Astier
Bernadette
B
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
Lambás Señas
Laura
L
Soulière
Fabienne
F
Schmitt
Patricia
P
Urbain
Nadia
N
Rentero
Nicolas
N
Bert
Lionel
L
Denoroy
Luc
L
Renaud
Bernard
B
Lesourd
Monique
M
Muñoz
Carmen
C
Chouvet
Guy
G
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
D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists; D013141:Spiro Compounds; C075319:alnespirone; D003000:Clonidine; D002065:Buspirone; D009638:Norepinephrine