(2) and Mihara and Fujimoto (3). In this study, [3H]-(+)-PN200 110 specific binding was competitively displaced by the two enantiomers in depolarized cerebral microvessels. The calculated K; values for S-312-d and S-312-1 were 0.12 and 2.4 nM, respectively. The antihypertensive effect of S-312-d in spontaneously hypertensive rats (SHR) was approximately 100 times stronger than that of S-312-1(4). In addition, a strong prophylactic effect on the occurrence of strokes in stroke prone SHR (SHRSP) and moderate therapeutic effects in diseased SHRSP were also observed by the daily oral administration of S-312-d (5). In these studies, the viability of the pyramidal cells in the hippo campus of surviving SHRSP was significantly increased by S-312-d. S-312-d seems to prevent the occurrence of cell death following a cerebral stroke by its calcium antagonistic effect. Since S-312-d seems to easily pass through the blood brain barrier because of its high lipophilicity (log P = 5.2, n-octanol/water), it should modify some physiological events related to the central nervous system. The present study examined the anticon vulsant effects of S-312-d in several convulsion models in mice.Male and female DBA/2 mice 3 weeks after birth at Aburahi and weighing 7 to 11 g were used in the experi ments. Each group consisted of 5 male and 5 female mice. Audiogenic stimulation (70-90 db) caused by an ultrason ic cleaner (B-32; Bronson, Danbury, CT, USA) was applied to each mouse for 1 min at 1 hr after the oral administration of the test compounds. Usually, following a wild running phase, generalized myoclonus and then tonic flexion and extension of mice were caused by an auditory stimulation. Respiratory arrest of mice was observed after the occur rence of tonic extension. The anticonvulsant effect was de termined by recording the tonic extension. ED50 values were calculated by the probit method. Anticonvulsant effects of S-312, S-312-d, S-312-1, nimodipine, nicardipine and nilvadipine, which were synthesized at Shionogi Research Laboratories, were compared with those of flun arizine (Sigma, St. Louis, MO, USA). S-312 and S-312-d, but not S-312-1, had anticonvulsant effects in DBA/2 mice. Dose-dependent anticonvulsant effects were ob served after the oral administration of S-312, S-312-d, nil vadipine and flunarizine (Fig. 1). Table 1 shows the ED50
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