Clinical potential of lomerizine, a Ca2+ channel blocker as an anti-glaucoma drug: effects on ocular circulation and retinal neuronal damage.
Glaucoma is defined as an optic neuropathy with characteristic changes in the optic nerve head and ultimate loss of visual field. Previous studies have suggested that (a) mechanical damage due to raised intraocular pressure and (b) a compromised tissue circulation in the optic nerve head play significant roles in the development of glaucomatous damage in the optic nerve head. Recently, we found that lomerizine, a new Ca(2+) channel blocker, increased ocular circulation and protected neuronal cells against retinal neurotoxicity both in vitro and in vivo with minimal cardiovascular side effects. We examined the effect of lomerizine on the ocular circulation and compared it with those of other Ca(2+) channel blockers in normal rabbits and in rabbits with an endothelin-1-disturbed circulation in the optic nerve head. In anesthetized rabbits, lomerizine and the other Ca(2+) channel blockers increased the ocular circulation and also inhibited the hypoperfusion induced in optic nerve head tissue by an intravitreous injection of endothelin-1. Whereas the other Ca(2+) channel blockers produced changes in blood pressure and heart rate, the effects of lomerizine on these parameters were slight. In healthy humans, lomerizine increased blood velocity in the optic nerve head, without significantly altering blood pressure or heart rate. Moreover, lomerizine reduced retinal damage in rats both in vitro and in vivo, presumably through a Ca(2+) channel blocking effect via an action that may involve a direct protection of retinal neurons as well as an improvement in the ocular circulation. These results indicate that lomerizine may be useful as a therapeutic drug against ischemic retinal diseases (such as glaucoma and retinal vascular occlusive diseases) that involve a disturbance of the ocular circulation.
Hara
Hideaki
H
Department of Biofunctional Molecules, Gifu Pharmaceutical University, 5-6-1 Mitahora-higashi, Gifu 502-8585, Japan. hidehara@gifu-pu.ac.jp.
Toriu
Nobuko
N
Shimazawa
Masamitsu
M
D000818:Animals; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D002560:Cerebrovascular Circulation / Q000187:drug effects; D002986:Clinical Trials as Topic; D005123:Eye / Q000098:blood supply*; D005901:Glaucoma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects; D008954:Models, Biological; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D009900:Optic Nerve / Q000187:drug effects / Q000473:pathology; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D012160:Retina / Q000187:drug effects* / Q000473:pathology; D012171:Retinal Vessels / Q000187:drug effects*
D002121:Calcium Channel Blockers; D010879:Piperazines; C052424:lomerizine