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F-0401 ((+/-)-(E)-3-[4-(1-imidazolyl)methylphenyl]-2-propen-1-yl methyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-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 KCl-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) &gt; coronary(6.9) &gt; 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 CaCl2 in the depolarized basilar artery (pA2 value: 8.9). However, the reductions of 5-HT and PGF2 alpha-induced contractions by F-0401 in this artery were very weak (pD'2 value:5.9 and &lt; 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 Ca2+ channels.

Pharmacological profile of F-0401, a novel dihydropyridine derivative. (2). The vasodilator action of F-0401 in isolated canine arteries.