Lomerizine, a Ca2+ channel blocker, reduces glutamate-induced neurotoxicity and ischemia/reperfusion damage in rat retina.

Abstract

We 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 7 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 microM) or flunarizine (1 microM) significantly reduced glutamate-induced neurotoxicity, the effects being concentration dependent. Lomerizine (1 microM) also exhibited protective effects against both the N-methyl-D-aspartate and kainate induced types of neurotoxicity. However, lomerizine (1 microM) had little effect on the neurotoxicity induced by ionomycin (1 microM) 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).

• Authors: N Toriu, A Akaike, H Yasuyoshi, S Zhang, S Kashii, Y Honda, M Shimazawa, H Hara
• Journal: Experimental eye research (Exp Eye Res) Vol. 70 Issue 4 Pg. 475-84 (Apr 2000) ISSN: 0014-4835 [Print] England
• PMID: 10865996 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Calcium Channel Blockers
• Neuroprotective Agents
• Piperazines
• Glutamic Acid
• Dizocilpine Maleate
• lomerizine
• Flunarizine

Topics

• Animals
• Calcium Channel Blockers (therapeutic use)
• Cells, Cultured
• Dizocilpine Maleate (therapeutic use)
• Dose-Response Relationship, Drug
• Flunarizine (therapeutic use)
• Glutamic Acid (adverse effects)
• Male
• Neuroprotective Agents (therapeutic use)
• Neurotoxicity Syndromes (drug therapy, etiology)
• Piperazines (therapeutic use)
• Rats
• Rats, Sprague-Dawley
• Reperfusion Injury (prevention & control)