[The alpha-antiadrenergic properties of spiroxatrine, a ligand of serotonergic 5-HT1A receptors].

The 5-HT1A ligand, spiroxatrine, displays very low affinity for alpha 1-adrenergic binding sites and a relatively high affinity for alpha 2-adrenergic binding sites. Nonetheless, recent functional studies indicate that spiroxatrine is a potent antagonist of the alpha 1-adrenoceptor mediating contraction in the rat isolated aorta. On the basis of the widely studied heterogeneous interaction of drugs with alpha-adrenoceptors in several experimental models, the present study was designed to analyze the alpha-adrenoceptor antagonist properties of spiroxatrine in the pithed rat. Animals were prepared for recording of arterial blood pressure and intravenous (i.v.) administration of drugs. Norepinephrine and the alpha 1- and alpha 2- adrenoceptor agonists methoxamine and clonidine, respectively, elicited pressor responses in a dose-related fashion. Spiroxatrine (1 mg/kg, i.v.) produced a moderate--but significant--rightward displacement of the dose-response curves to all agonists. The present data lead us to suggest that, though spiroxatrine exhibits alpha 1- and alpha 2-adrenoceptor antagonist properties in the pithed rat, its potency does not seem to correlate with that found in rat aorta. The potential involvement of alpha 1-adrenoceptor subtypes is discussed.