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Abstract #5836 Published in IGR 2-1
Lomerizine, a Ca2+ channel blocker, reduces glutamate-induced neurotoxicity and ischemia/reperfusion damage in rat retina
Toriu N; Akaike A; Yasuyoshi H; Zhang S; Kashii S; Honda Y; Shimazawa M; Hara HExperimental Eye Research 2000; 70: 475-484
The authors examined the effects of a new Ca2+ channel blocker, lomerizine, on the intraocular hypertension-induced ischemia/reperfusion injury in rat retina and on the glutamate-induced neurotoxicity in rat cultured retinal neurons, and compared its effects with those of a Ca2+ channel blocker (flunarizine) and an N-methyl-D-aspartate receptor antagonist (MK-801). Morphometric evaluation at seven days after ischemia/reperfusion showed that treatment with lomerizine (0.1 and 1 mg kg-1, i.v.) prior to ischemia and again immediately after reperfusion dose-dependently reduced the retinal damage. Treatment with MK-801 (1 mg kg-1, i.v.) before ischemia significantly reduced the resulting retinal damage. Flunarizine (0.1 and 1 mg kg-1, i.v.) tended to reduce the retinal damage, but its effect did not reach statistical significance. In an in vitro study, pretreatment with lomerizine (0.1 and 1 μm) or flunarizine (1 μm) significantly reduced glutamate-induced neurotoxicity, the effects being concentration dependent. Lomerizine (1 μm) also exhibited protective effects against both the N-methyl-D-aspartate and kainate induced types of neurotoxicity. However, lomerizine (1 μm) had little effect on the neurotoxicity induced by ionomycin (1 μm) application. Glutamate-induced neurotoxicity was abolished by removing Ca2+ from the medium. These results indicate that lomerizine protects neuronal cells against retinal neurotoxicity both in vivo and in vitro, and that this Ca2+ channel blocker may be useful as a therapeutic drug against retinal diseases that cause neuronal injury, such as normal tension glaucoma (NTG).
Dr. H. Hara, Pharmacology Group, R&D Laboratories, Nippon Organon K.K., 1-5-90, Tomobuchi-cho, Miyakojima-ku, Osaka, 534-0016, Japan. email: hidehara@tim.hi-ho.ne.jp
Classification:
11.8 Neuroprotection (Part of: 11 Medical treatment)
