[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.
Terrón
J A
JA
Departamento de Farmacología y Toxicología, Centro de Investigación y de Estudios Avanzados, Instituto Politécnico Nacional, México, D.F.
Ibarra
M
M
Ransanz
V
V
Hong
E
E
Villalón
C M
CM
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine / Q000494:pharmacology; D003655:Decerebrate State / Q000503:physiopathology; D004146:Dioxanes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008024:Ligands; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects*; D013141:Spiro Compounds / Q000494:pharmacology*
D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D008024:Ligands; D011985:Receptors, Serotonin; D013141:Spiro Compounds; C018387:spiroxatrine; D008729:Methoxamine; D003000:Clonidine; D009638:Norepinephrine
Propiedades antiadrenérgicas alfa de la espiroxatrina, un ligando de los receptores serotonérgicos 5-HT1A.