Bronzetti E, Felici L, Polidori C, Amenta F
Dipartimento di Scienze Cardiovascolari e Respiratorie, Università La Sapienza, Roma, Italy.
J Auton Pharmacol. 1994 Apr;14(2):79-85. doi: 10.1111/j.1474-8673.1994.tb00592.x.
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.
本研究旨在评估二氢吡啶类（非洛地平、尼卡地平、硝苯地平、尼莫地平、尼群地平和尼索地平）以及苯烷基胺类（维拉帕米）的钙通道阻滞剂是否对α-肾上腺素能受体与人类右冠状动脉和乳腺动脉切片的结合有任何影响，该结合使用[3H]-二氢麦角隐亭（DHT）作为配体进行测量。尼卡地平、维拉帕米和尼群地平浓度的增加与[3H]-DHT与人类冠状动脉和乳腺动脉切片的结合竞争。所测试的其他化合物则无此作用。在[3H]-DHT结合的竞争者中，尼卡地平最为强效，其50%抑制（IC50）值约为10 nM。在存在或不存在三磷酸鸟苷和氯化钠的情况下，尼卡地平与[3H]-DHT结合竞争的药理学特征与二氢吡啶衍生物在α-肾上腺素能受体处的拮抗剂活性一致。与心血管治疗中使用的其他钙通道阻滞剂相比，这一特性可能解释了尼卡地平引起的较低交感神经刺激活性。
