Effects of Semotiadil,A Novel Calcium Antagonist,on the Retina and Optic Nerve Head Circulation

ABSTRACT

The effects of semotiadil, a novel benzothiazine calcium antagonist, on the retinal and optic nerve head (ONH) tissue circulation were evaluated using the noninvasive laser speckle method. In urethane-anesthetized Dutch or albino rabbits, before and up to 90 min following intravenous injection of 400 μg/kg semotiadil fumarate (semotiadil group) or vehicle (control group), normalized blur value, a quantitative index of tissue blood velocity, in the retina (NB_retina) or ONH (NB_onh), was serially obtained with monitoring intraocular pressure (IOP) and systemic parameters: arterial pressure, pulse rate, arterial blood gas, and body temperature. There were no significant differences in IOP and the systemic parameters except arterial pressure between semotiadil and control groups during the experiments. Arterial pressure showed an acute and transient drop during the first 5 min after semotiadil administration. The time courses of the normalized blur value were significantly different between semotiadil and control groups in the retina (P=0.0001, repeated measures two-way ANOVA), but not in the ONH (P = 0.6724). Changes in NB_retina from the baseline in the semotiadil group was significantly greater than those in the control group 50 min or later after the administration (P < 0.0500, Mann-Whitney test). NB_onh showed no significant differences between the two groups except during the first few min when arterial pressure acutely decreased in the semotiadil group. In conclusion, intravenously injected semotiadil increased the tissue blood velocity in the retina, but not in the ONH. This vascular selectivity in the ocular neural tissues differs from those of other calcium antagonists, such as nicardipine.