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  • Title: In vivo comparison of two 5-HT1A receptors agonists alnespirone (S-20499) and buspirone on locus coeruleus neuronal activity.
    Author: Astier B, Lambás Señas L, Soulière F, Schmitt P, Urbain N, Rentero N, Bert L, Denoroy L, Renaud B, Lesourd M, Muñoz C, Chouvet G.
    Journal: Eur J Pharmacol; 2003 Jan 10; 459(1):17-26. PubMed ID: 12505530.
    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.
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