Effect of calcium channel blockers alone and in combination with antiglaucoma medications on intraocular pressure in the primate eye

Purpose: To determine the effect of representative members from six classes of calcium channel blockers on intraocular pressure in the primate eye. Ot her antiglaucoma medications were administered with verapamil to determine their combined effect on intraocular pressure. Methods: Six healthy cynomolgus monkeys were anesthetized, and baseline int raocular pressure was measured. Drug-containing solution (50 mu L) was inst illed in one eye and intraocular pressure was measured in both eyes 90 minu tes later. Results: All classes of calcium channel blockers significantly lowered intr aocular pressure in the treated eye. The percent reduction in intraocular p ressure compared with the baseline pressure was 10% for verapamil (P < 0.00 2), 18% for nifedipine (P < 0.001), 15% for diltiazem (P < 0.001), 17% for flunarizine (P < 0.001). 19% for prenylamine (P < 0.001), and 6% for perhex iline (P < 0.01). In the fellow eye, a significant reduction in intraocular pressure was also seen with all calcium channel blockers except perhexilin e, which suggested a crossover effect. In contrast, neither vehicle treated nor contralateral eyes showed a lowering of intraocular pressure when test ed under the same conditions. In the treated eye, 0.5% timolol (P < 0.01) a nd 0.05% clonidine (P < 0.02) combined with 0.25% verapamil each appeared t o produce an additive effect. with a significantly greater pressure-lowerin g effect than either agent alone. In addition, 0.005% pilocarpine (P < 0.00 1) and 0.00125% demecarium (P < 0.01) combined with 0.25% verapamil each ap peared to produce a synergistic effect, with a significantly greater reduct ion in intraocular pressure than both agents combined. Conclusions: Topical calcium channel blockers and combinations of verapamil with antiglaucoma medications may provide a useful alternative for reducin g intraocular pressure in patients with ocular hypertension or primary open -angle glaucoma.