Cerebrovascular effects of the calcium antagonistic dihydropyridine derivative nimodipine in animal experiments

Abstract

Isopropyl(2-methoxy-ethyl) 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate (Bay e 9736, nimodipine) is a calcium antagonistic dihydropyridine derivative with a preferential effect on cerebral vessels. It dilates cerebral vessels in several species after intraarterial, intravenous, perlingual, and oral administration in low dosage. Its effect on the peripheral blood vessels is less pronounced so that nimodipine increases cerebral blood flow without substantial decrease of blood pressure. Nimodipine does not inhibit carbonic anhydrase and does not stimulate the oxygen consumption of brain tissue in vitro. Its effect is not influenced by propranolol. Therefore its cerebral vasodilating effect is due to its direct relaxing effect on vascular smooth muscle. Nimodipine prevents the postischaemic impaired cerebral reperfusion in cats. Transient global cerebral ischaemia increases the cerebrovascular resistance to flow by means of the increase in extracellular concentration of potassium ions. Such depolarization produces sustained cerebral vasoconstriction presumably by enhancing transmembrane influx of calcium. Nimodipine does not influence the ischaemic increase in Ko+ ions but effectively prevents the postischaemic cerebrovascular spasm. From its pharmacological properties nimodipine is predicted to be effective in the prevention and therapy of cerebrovascular spasm of various origins and especially in the treatment of postischaemic brain damage.