Effect of a novel calcium antagonist AE0047 on several models of cerebral ischemia

Abstract

AbstractWe examined the cerebral protective effects of AE0047 employing cerebral ischemia models. In the bilateral carotid arterial occlusion model (BCAO) employing spontaneously hypertensive rats (SHRs), oral administration of AE0047 (0.1–0.3 mg/kg) or nicardipine (3 mg/kg) improved the neurological symptoms by 2 hr after the BCAO procedure and energy metabolite changes 30 min after the BCAO procedure. AE0047 was significantly effective in these 2 models at one‐tenth the dosage of nicardipine. Dihydroergotoxine completely protected in an adrenaline‐induced lethality model. AE0047 also showed a protective action in this model and is considered to have an α‐adrenergic blocking action similar to dihydroergotoxine. In the KCN‐induced abnormal behavior (the coma and the disappearance of searching behavior) and death models, protective effects were observed in the AE0047 group, but not in the nicardipine group. Protective action was marked even 2–4 hr after AE0047 administration. Dihydroergotoxine also shortened the duration of coma and prolonged the survival time, but had no effect on mortality. From these results, it is suggested that the α‐adrenergic blocking action of AE0047 participates in the antihypertensive action. The protective effects of AE0047 were most striking at 2 and 4 hr after AE0047 administration. © 1992 Wiley‐Liss, Inc.