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 aqueous 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 reported the ocular hypotensive effect of topical nifedipine and verapamil in albino rabbits, the original aim of the present work was to evaluate 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 were carried out in two stages. In the first one, short term effects of topical diltiazem on intraocular pressure were studied in groups of 13 albino rabbits receiving 8 different doses of the drug in order to obtain a dose-response curve. Tonographies were performed in 13 anaesthetized animals before and 90min after drug instillation. In a second phase, the persistence of the effect of diltiazem on intraocular pressure was examined in 6 groups of 10 rabbits each receiving three different doses of the drug. Topical diltiazem was found to lower intraocular pressure in a dose-related fashion. The maximum response to diltiazem was greater and the ED₅₀ lower than those previously reported for nifedipine 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 days. Due to the intensity and the persistence of its intraocular pressure-lowering effect, diltiazem shows great potential for the treatment of glaucoma, since a daily or less frequent administration may be enough to control ocular hypertension. Received: 23 October 1996 / Accepted: 5 February 1997