Neuroprotection by lomerizine, a prophylactic drug for migraine, against hydrogen peroxide-induced hippocampal neurotoxicity.

Migraine is one of the risk factor for ischemic stroke. The purpose of this study was to examine the effect of lomerizine, a prophylactic drug for migraine, on HO-induced cell death of hippocampal neurons. Cytosolic Ca concentration was measured using fura-2 as a Ca indicator. Cell death was estimated by trypan blue exclusion. In rat-cultured hippocampal neurons, the addition of HO induced biphasic Ca elevations and cell death. The HO-induced biphasic Ca elevations and cell death only occurred when extracellular Ca was present. The biphasic Ca elevation was mediated by Ca influx through the plasma membrane, but not Ca release from the intracellular Ca store. Both the early and late phases of HO-induced Ca influx were reduced by either a T- or L-type voltage-dependent Ca channel (VDCC) blocker, lomerizine. In fact, L-type VDCC (α subunit) and T-type VDCC (α subunit) mRNA were expressed in rat hippocampal neurons. Although an L-type VDCC blocker, nifedipine, partly suppressed the late phase of Ca influx in response to HO, a T-type VDCC blocker, mibefradil, reduced both phases of Ca influx. Moreover, lomerizine and mibefradil strongly reduced HO-induced cell death, and nifedipine weakly reduced it. These findings suggest that the inhibition of HO-induced Ca influx through T-type VDCC seems to be important in the protective effect of lomerizine against oxidative stress. It is possible that lomerizine may be a useful drug for prophylactic treatment of migraine, because migraine is a risk factor for ischemic stroke. [ABSTRACT FROM AUTHOR]