Effect of calcium channel blockers alone and in combination with antiglaucoma medications on intraocular pressure in the primate eye.
OBJECTIVE
To determine the effect of representative members from six classes of calcium channel blockers on intraocular pressure in the primate eye. Other antiglaucoma medications were administered with verapamil to determine their combined effect on intraocular pressure.


METHODS
Six healthy cynomolgus monkeys were anesthetized, and baseline intraocular pressure was measured. Drug-containing solution (50 microL) was instilled in one eye and intraocular pressure was measured in both eyes 90 minutes later.


RESULTS
All classes of calcium channel blockers significantly lowered intraocular pressure in the treated eye. The percent reduction in intraocular pressure compared with the baseline pressure was 10% for verapamil (P < 0.002), 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 perhexiline (P < 0.01). In the fellow eye, a significant reduction in intraocular pressure was also seen with all calcium channel blockers except perhexiline, which suggested a crossover effect. In contrast, neither vehicle treated nor contralateral eyes showed a lowering of intraocular pressure when tested under the same conditions. In the treated eye, 0.5% timolol (P < 0.01) and 0.05% clonidine (P < 0.02) combined with 0.25% verapamil each appeared to produce an additive effect, with a significantly greater pressure-lowering effect than either agent alone. In addition, 0.005% pilocarpine (P < 0.001) and 0.00125% demecarium (P < 0.01) combined with 0.25% verapamil each appeared to produce a synergistic effect, with a significantly greater reduction 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 reducing intraocular pressure in patients with ocular hypertension or primary open-angle glaucoma.
Siegner
S W
SW
Department of Ophthalmology, Emory University, Atlanta, Georgia, USA.
Netland
P A
PA
Schroeder
A
A
Erickson
K A
KA
D000818:Animals; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D005901:Glaucoma / Q000188:drug therapy* / Q000503:physiopathology; D007429:Intraocular Pressure / Q000187:drug effects* / Q000502:physiology; D008252:Macaca fascicularis; D008297:Male; D008916:Miotics / Q000008:administration & dosage / Q000494:pharmacology*; D009883:Ophthalmic Solutions; D010862:Pilocarpine / Q000008:administration & dosage / Q000494:pharmacology*; D000644:Quaternary Ammonium Compounds / Q000008:administration & dosage / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D008916:Miotics; D009883:Ophthalmic Solutions; D000644:Quaternary Ammonium Compounds; D010862:Pilocarpine; C100193:demecarium