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-HT1A receptor agonist, alnespirone (S-20499), with those of buspirone, a 5-HT1A 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 mug/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. (C) 2002 Elsevier Science B.V. All rights reserved.