Ichihara K, Okumura K, Mori H, Nagasaka M
Department of Pharmacology, Maruko Pharmaceutical Co., Ltd., Kasugai, Japan.
Eur J Pharmacol. 1993 Jul 20;238(2-3):283-9. doi: 10.1016/0014-2999(93)90858-f.
MPC-1304 is a novel Ca2+ entry blocker of the 1,4-dihydropyridine type. In the present study, the effect of oral administration of MPC-1304 on alpha-adrenoceptor-mediated pressor responses was examined in pithed rats and compared with that of nifedipine. Drugs were administered orally to conscious animals before pithing. MPC-1304 (0.3-3 mg/kg) and nifedipine (1-10 mg/kg) inhibited pressor responses to norepinephrine, phenylephrine (alpha 1-adrenoceptor agonist), UK-14304 (alpha 2-adrenoceptor agonist), and sympathetic nerve (spinal cord segments) stimulation. MPC-1304 was roughly 3 times more potent than nifedipine in inhibiting these responses. The inhibitory effect of MPC-1304 (3 mg/kg) on the pressor response to UK-14304 lasted longer than that of nifedipine (3 mg/kg). At the same time, plasma concentrations of MPC-1304 were lower than those of nifedipine. These results suggest that MPC-1304 has a great ability to inhibit pressor responses to norepinephrine and peripheral sympathetic stimulation after its oral administration, and that this effect of MPC-1304 is closely correlated with its potent antihypertensive activity.
MPC - 1304是一种新型的1,4 - 二氢吡啶类钙通道阻滞剂。在本研究中，在脊髓毁损大鼠中检测了口服MPC - 1304对α - 肾上腺素能受体介导的升压反应的影响，并与硝苯地平进行了比较。在脊髓毁损前，给清醒动物口服给药。MPC - 1304（0.3 - 3毫克/千克）和硝苯地平（1 - 10毫克/千克）抑制了对去甲肾上腺素、苯肾上腺素（α1 - 肾上腺素能受体激动剂）、UK - 14304（α2 - 肾上腺素能受体激动剂）以及交感神经（脊髓节段）刺激的升压反应。在抑制这些反应方面，MPC - 1304的效力约为硝苯地平的3倍。MPC - 1304（3毫克/千克）对UK - 14304升压反应的抑制作用比硝苯地平（3毫克/千克）持续时间更长。同时，MPC - 1304的血浆浓度低于硝苯地平。这些结果表明，MPC - 1304口服后具有很强的抑制对去甲肾上腺素和外周交感神经刺激的升压反应的能力，并且MPC - 1304的这种作用与其强大的降压活性密切相关。
