Interactions between calcium channel blockers and alpha-adrenoceptors in the human coronary and mammary arteries: a radioligand binding study.
The study was designed to assess whether Ca2+ channel blockers of the dihydropyridine family (felodipine, nicardipine, nifedipine, nimodipine, nitrendipine and nisoldipine), and of the phenylalkylamine family (verapamil) have any effect on alpha-adrenoceptor binding to sections of the human right coronary and mammary arteries, measured using [3H]-dihydroergocryptine (DHT) as a ligand. Increasing concentrations of nicardipine, verapamil and nitrendipine competed with [3H]-DHT binding to sections of the human coronary and mammary arteries. The other compounds tested were without effect. Among the competitors of [3H]-DHT binding, nicardipine was the most powerful, with a 50% inhibition (IC50) value of approximately 10 nM. The pharmacological profile of competition with [3H]-DHT binding by nicardipine, in the presence or in the absence of guanosine triphosphate and NaCl, is consistent with antagonist activity of the dihydropyridine derivative at the alpha-adrenoceptor. This property may account for the lower sympathetic stimulatory activity elicited by nicardipine, in comparison with other Ca2+ channel blockers used in cardiovascular therapy.
Bronzetti
E
E
Dipartimento di Scienze Cardiovascolari e Respiratorie, Università La Sapienza, Roma, Italy.
Felici
L
L
Polidori
C
C
Amenta
F
F
D000293:Adolescent; D000328:Adult; D001667:Binding, Competitive / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism*; D004088:Dihydroergotoxine / Q000493:pharmacokinetics; D005260:Female; D006160:Guanosine Triphosphate / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008323:Mammary Arteries / Q000187:drug effects / Q000378:metabolism*; D011869:Radioligand Assay; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D014700:Verapamil / Q000493:pharmacokinetics
D002121:Calcium Channel Blockers; D011942:Receptors, Adrenergic, alpha; D004088:Dihydroergotoxine; D006160:Guanosine Triphosphate; D014700:Verapamil