新規ジヒドロピリジン誘導体F-0401の薬理作用-2-イヌ摘出血管に対する作用

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F-0401 ((+) - (E) -3- [4- (1-imidazolyl) methylphenyl] -2-propen-l-y1 methyl 1, 4-dihydro-2, 6-dimethyl-4- (3-nitropheny1) -3, 5-pyridinedicarboxylate) is a newly synthesized dihydropyridine derivative. We investigated the vasodilator action of F-0401 in isolated canine cerebral and peripheral arteries. F-0401 reduced KC1-induced contraction of the arteries in a concentration-dependent manner. The inhibitory action on cerebral arteries was greater than that on the peripheral ones. Its pD'2 values were as follows : Middle cerebral (8.3), basilar (8.1) > coronary (6.9) > femoral, renal, internal carotid, vertebral, mesenteric (6.0-5.5) arteries. The cerebrovascular-selectivity (the ratio of the pD'2 of the basilar artery to that of the femoral one) of F-0401 was 4, 25 and 40 times as large as that of flunarizine, nicardipine and nimodipine, respectively. F-0401 shifted to the right the concentration-response curve for CaCl 2 in the depolarized basilar artery (pA 2 value : 8.9). However, the reductions of 5-HT and PGF 2α-induced contractions by F-0401 in thisartery were very weak (pD'2 value : 5.9 and <4.5). These results suggest that F-0401 is a potent cerebrovascular-selective vasodilator and its effects were attributed to the inhibitory effect on the voltage-dependent Ca 2+ channels.
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