Effects of Lomerizine, a Novel Ca²⁺Channel Blocker, on the Normal and Endothelin-1-disturbed Circulation in the Optic Nerve Head of Rabbits

Abstract

We examined the effects of lomerizine, a new diphenylmethylpiperazine Ca2+ channel blocker, on the normal circulation in the optic nerve head and long posterior ciliary artery, and on endothelin-1-induced hypoperfusion in the optic nerve head in anesthetized rabbits using a hydrogen gas clearance method and laser Doppler flowmetry. These effects were compared with those of nilvadipine and pranidipine. Lomerizine (0.1 and 0.3 mg/kg, i.v.) significantly increased tissue blood flow in the optic nerve head and the putative blood flow in the long posterior ciliary artery with smaller reduction of blood pressure (0.3 mg/kg, i.v.) and without change in heart rate. On the other hand, nilvadipine (0.003 and 0.01 mg/kg, i.v.) and pranidipine (0.003 and 0.01 mg/kg, iv.) each significantly increased blood flow and lowered blood pressure. Moreover, lomerizine (0.1 and 0.3 mg/kg, i.v.) and nilvadipine (0.01 mg/kg, i.v.), when administered 5 min before an endothelin-1 injection (10(-6) M, 100 microl), inhibited the hypoperfusion in the optic nerve head. These results suggest that lomerizine improves the ocular circulation with minimal cardiovascular side effects. Therefore, lomerizine may have clinical potential for the treatment of eye diseases associated with local circulatory disturbances, such as normal-tension glaucoma.

Lomerizine, a Ca2+Channel Blocker, Reduces Glutamate-induced Neurotoxicity and Ischemia/Reperfusion Damage in Rat Retina

“…Brovincamine and nimodipine, both Ca# + channel blockers, have been reported to have a favorable effect on the visual field in patients with NTG (Bose, Piltz and Breton, 1995 ;Sawada et al, 1996), although the mechanism underlying this improvement is not fully understood. Recently, lomerizine has been reported to increase blood flow in the ONH in conscious rabbits without affecting systemic hemodynamics , and to inhibit the hypoperfusion seen in ONH tissue in anesthetized rabbits after the intravitreous injection of endothelin-1 (Toriu et al, 1999). These findings seem to suggest that the protective effect of lomerizine against retinal ischemic injury is due to an improvement in the ocular circulation.…”

Extraocular Blood Flow and Endothelin-1 Plasma Levels in Patients with Multiple Sclerosis

“…Even though clinical consequences from this study should be drawn with caution, additional therapy with calcium channel blockers [34, 35]or, possibly in the future, with ET-1 receptor blockers, might be beneficial in MS patients.…”

Magnesium: Effect on ocular health as a calcium channel antagonist

“…Indeed, increased ET-1 level was associated with glaucoma progression despite normal IOP level [46]. ET-1 induces contraction of retinal and optic nerve head vessels, which is dependent on an influx of extracellular calcium through voltage-gated calcium channels, and then resulting in decreased ocular blood flow and ischemia [47][48][49][50][51][52]. Efficacy of ET-1 can be inhibited by calcium channel blockade.…”

“…So that calcium channel blockers were evaluated for the management of glaucoma. In this sense, some calcium channel blockers have shown a positive effect on ocular blood flow and visual field in NTG [50,53,54]. But many systemic side effects such as hypotension, bradycardia, conduction disturbances and decrease in cardiac output can be seen during the calcium channel blocker intake, resulting in a restriction in the use for chronic diseases such as NTG [55].…”