Effect of lomerizine, a new Ca2+ channel blocker, on the microcirculation in the optic nerve head in conscious rabbits: a study using a laser speckletechnique

We examined the effect of a new Ca2+ channel blocker, lomerizine (KB-2796), and compared it with that of nilvadipine, on the optic nerve head circulat ion in conscious rabbits using a laser speckle method. Lomerizine (0.03, 0. 1 and 0.3 mg kg(-1), i.v.) and nilvadipine (0.003, 0.01 and 0.03 mg kg(-1), i.v.) each significantly increased the normalized blur Values (an index of tissue blood velocity) in the optic nerve head in a dose-dependent manner. Neither lomerizine nor nilvadipine caused a significant change in intraocu lar pressure. Lomerizine produced no significant change in mean arterial bl ood pressure, although at 0.3 mg kg(-1), i.v. heart rate was significantly increased 5 min after its administration. In contrast, nilvadipine signific antly decreased mean arterial blood pressure at 5 to 15 min after its admin istration and increased heart rate at 5-30 min after its administration (bo th effects being dose-dependent). Our results indicate that while lomerizin e, like nilvadipine, increased tissue blood velocity in the optic nerve hea d, it did not affect mean arterial blood pressure at the doses that affecte d optic nerve head circulation, unlike nilvadipine. The plasma concentratio n of lomerizine (free base) obtained from rabbits at 15 min after administr ation at a dose of 0.03 mg kg(-1) i.v., when time there was a significant i ncrease in tissue blood velocity in the optic nerve head, was very similar to plasma concentration with healthy subjects receiving lomerizine at 10 mg (5 mg x 2) day(-1), p.o., a dose that achieved a significant reduction in the frequency and mean duration of headache attacks but did not affect the blood pressure or heart rate. These results suggest that lomerizine may be clinically effective in favorably affecting the optic nerve circulation wit hout producing systemic effects such as the hypotension seen during treatme nt with other Ca2+ channel blockers. (C) 1999 Academic Press.