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Lomerizine, a Ca2+ channel blocker, reduces glutamate-induced neurotoxicity and ischemia/reperfusion damage in rat retina.
- Source :
-
Experimental eye research [Exp Eye Res] 2000 Apr; Vol. 70 (4), pp. 475-84. - Publication Year :
- 2000
-
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).
- Subjects :
- Animals
Cells, Cultured
Dizocilpine Maleate therapeutic use
Dose-Response Relationship, Drug
Flunarizine therapeutic use
Male
Neuroprotective Agents therapeutic use
Neurotoxicity Syndromes etiology
Rats
Rats, Sprague-Dawley
Calcium Channel Blockers therapeutic use
Glutamic Acid adverse effects
Neurotoxicity Syndromes drug therapy
Piperazines therapeutic use
Reperfusion Injury prevention & control
Subjects
Details
- Language :
- English
- ISSN :
- 0014-4835
- Volume :
- 70
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Experimental eye research
- Publication Type :
- Academic Journal
- Accession number :
- 10865996
- Full Text :
- https://doi.org/10.1006/exer.1999.0809