A LONG-LASTING HYPOTENSIVE EFFECT OF TOPICAL DILTIAZEM ON THE INTRAOCULAR-PRESSURE IN CONSCIOUS RABBITS

The effect of calcium channel blockers on intraocular pressure and aqu eous humor dynamics remains still controversial, although preliminary evidence suggests that these drugs may be beneficial in the management of ocular hypertension and low-tension glaucoma. Having previously re ported the ocular hypotensive effect of topical nifedipine and verapam il in albino rabbits, the original aim of the present work was to eval uate the effect of topical diltiazem on aqueous humor dynamics in this species. Intraocular pressure was measured with a manual applanation tonometer. The experiments examining the ocular actions of diltiazem w ere carried out in two stages. In the first one, short term effects of topical diltiazem on intraocular pressure were studied in groups of 1 3 albino rabbits receiving 8 different doses of the drug in order to o btain a dose-response curve. Tonographies were performed in 13 anaesth etized animals before and 90 min after drug instillation. In a second phase, the persistence of the effect of diltiazem on intraocular press ure was examined in 6 groups of 10 rabbits each receiving three differ ent doses of the drug. Topical diltiazem was found to lower intraocula r pressure in a dose-related fashion. The maximum response to diltiaze m was greater and the ED50 lower than those previously reported for ni fedipine and verapamil. In the tonographic study, diltiazem was shown to reduce the facility of aqueous humor outflow and inflow. Diltiazem exhibited a long lasting effect on intraocular pressure that was again dose-related. Depending on the dose administered, the calculated time necessary for the peak effect to be halved ranged from 0.6 to 7.0 day s. Due to the intensity and the persistence of its intraocular pressur e-lowering effect, diltiazem shows great potential for the treatment o f glaucoma, since a daily or less frequent administration may be enoug h to control ocular hypertension.