Vascular effects of ipsapirone are related with subtypes of alpha 1-adrenergic receptors.
The aim of this study was to provide further evidence about the participation of alpha 1-adrenoceptors in the vascular responses elicited by ipsapirone. This 5-HT1A agonist displayed vasodilator activity only when aortic rings were precontracted by alpha-adrenergic compounds. The relaxant effect was particularly evident when rings were precontracted with methoxamine (selective alpha 1A-adrenergic agonist). On the other hand, ipsapirone but not chloroethylclonidine (selective alpha 1B-adrenergic antagonist), clearly displaced norepinephrine and methoxamine vasocontractile concentration-response curves to the right. Finally, ipsapirone protected the alpha-adrenoceptors form the irreversible blockade provoked by phenoxybenzamine, as judged by the norepinephrine contraction and stimulated phosphatidylinositil labeling. Accordingly the relaxant effect elicited by ipsapirone in aortic rings precontracted with alpha-adrenergic agonists and the protective action against blockade by phenoxybenzamine shown by this agent are proof of its ability to occupy alpha 1-adrenoceptors. Specifically, alpha 1A-adrenergic receptors seem to be involved in ipsapirone vascular effects, since this agent selectively relaxed aortic preparation precontracted with methoxamine and unlike chloroethylclonidine, clearly inhibited the contractile effect of this agonist. In summary, the present findings can be explained by accepting that ipsapirone may act as an antagonist at alpha 1A-adrenoceptors.
Castillo
C
C
Escuela Superior de Medicina del IPN, México, D.F.
Ibarra
M
M
Maŕquez
A J
AJ
Villalobos-Molina
R
R
Hong
E
E
D058668:Adrenergic alpha-1 Receptor Antagonists; D000818:Animals; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology*; D011817:Rabbits; D018340:Receptors, Adrenergic, alpha-1 / Q000145:classification; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects
D058668:Adrenergic alpha-1 Receptor Antagonists; D011743:Pyrimidines; D018340:Receptors, Adrenergic, alpha-1; D017366:Serotonin Receptor Agonists; C043077:ipsapirone; D008729:Methoxamine; D009638:Norepinephrine