Alpha-adrenoceptor antagonistic and calcium antagonistic effects of nicergoline in the rat isolated aorta.
The activity of the alpha-adrenoceptor antagonist nicergoline, a molecule composed of two constituent parts, ergoline and bromonicotinic acid, was investigated in the rat isolated aorta. Nicergoline (10 nM-0.1 microM) displaced concentration-effect curves elicited by noradrenaline and phenylephrine to the right and inhibited maximal responses elicited by both alpha-adrenoceptor agonists without significantly affecting prostaglandin F2 alpha-induced contractions. Higher concentrations of nicergoline (1 microM-50 microM) displaced to the right the concentration-effect curves elicited by calcium in a depolarizing medium. This calcium antagonist activity was not shared by either of the constituent parts. Nicergoline 100 microM abolished the 45Ca influx induced into rat aorta by 100 mM K+-containing physiological solution. The selectivity of nicergoline for alpha 1-adrenoceptors seen in binding experiments also depends on the presence of the bromonicotinic moiety of the molecule. It is concluded that nicergoline, but not its substituent parts, displays both alpha 1-adrenoceptor and calcium antagonism. The latter property may account for some of the observed effects of this compound.
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000502:physiology; D002118:Calcium / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015237:Dinoprost; D004873:Ergolines / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D009530:Nicergoline / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011460:Prostaglandins F / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects
D004873:Ergolines; D011460:Prostaglandins F; D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; D015237:Dinoprost; D009530:Nicergoline; D002118:Calcium; D009638:Norepinephrine