Clinical Potential of Lomerizine, a Ca²⁺ Channel Blocker as an Anti‐Glaucoma Drug: Effects on Ocular Circulation and Retinal Neuronal Damage

Abstract

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.

Calcium Channels as Novel Therapeutic Targets for Ovarian Cancer Stem Cells

“…Of the four selected compounds, manidipine, lacidipine, and benidipine target L-type calcium channels and are clinically used as antihypertensive agents [34], whereas lomerizine targets both Land T-type calcium channels and is generally used in the clinical treatment of migraines [35], as well as the experimental treatment of glaucoma and optic nerve injury [36].…”

Ocular perfusion pressure in glaucoma

“…Specific antihypertensive agents could have different effects on POAG. In vitro and in vivo studies with rabbits suggested that calcium channel antagonists may increase ocular circulation and protect neuronal cells against retinal neurotoxicity (Hara et al 2004). In patients with ocular vasospasm and normal tension glaucoma, the use of calcium channel antagonist agents was suggested to reduce vasospasm in some publications (Gaspar et al 1994;Schmidt et al 1996).…”

Lomerizine, a Ca2+ Channel Blocker, Protects against Neuronal Degeneration within the Visual Center of the Brain after Retinal Damage in Mice

“…To assess the protective effects of lomerizine against neuronal loss in dorsal LGN (dLGN) and SC, sections stained with cresyl violet were used for neuronal cell counting: six sections for dLGN (L1: bregma −1.70 mm, L2: −1.92 mm, L3: −2.14 mm, L4: −2.36 mm, L5: −2.58 mm, and L6: −2.80 mm) and four for SC (S1: bregma −3.30 mm, S2: −3.52 mm, S3: −3.74 mm, and S4: −3.96 mm) in each mouse ( Figure 1). The area of each field used for this cell counting was 0.036 mm 2 ( Figure 1C & E). Cell counts were carried out under a microscope at 400× magnification in a masked fashion by a single observer (Y.…”