title: Ocular effects of topical administration of the phosphodiesterase III inhibitor milrinone in rabbits and cats.
abstract: Increases in intracellular cAMP levels have previously been shown to decrease intraocular pressure (IOP) and increase ocular blood flow (OBF). However, the ocular effects of milrinone, which increases intracellular cAMP levels via selective cAMP PDE III inhibition, have not been investigated. The purpose of this study was to investigate the ocular effects of topically administered milrinone at different concentrations in rabbits and cats. When compared to vehicle in conscious rabbits, topical administration of milrinone at 0.03% decreased IOP (-14.1 +/- 2.6% vs. -7.4 +/- 3.7%, max. changes expressed as mean +/- SEM), at 0.1% increased IOP (10.4 +/- 8.5% vs. -1.7 +/- 4.1%), and at 0.01% and 1% did not significantly affect IOP. Neither pupil size nor central corneal thickness were affected by milrinone. Additionally, there were no signs of inflammation and no effects on corneal clarity. In anesthetized cats, topical administration of milrinone at 0.01-0.3% increased OBF (38.9 +/- 6.0% for milrinone vs. -7.4 +/- 4.4% for vehicle), and at 0.03%-0.3% decreased mean arterial pressure (-19.0 +/- 5.6 vs. 3.0 +/- 4.1 mmHg) in a dose-related manner. The durations of OBF enhancement (1.5-2.5 h) and MAP reduction (less than 30 min to 2 h) were also dose-dependent. In conclusion, milrinone induced biphasic IOP effects: IOP was decreased at 0.03% but increased at 0.1%. Milrinone at 0.01% increased OBF, possibly via a local vasodilator effect, and at 0.03-0.3% increased OBF, possibly via local and systemic effects. These data suggest that cAMP PDE III inhibitors such as milrinone may have efficacy as agents which enhance ocular blood flow following topical ocular application.
authors.affiliation: Sterling Winthrop Pharmaceuticals Research Division, Rensselaer, NY.
authors.forename: K C
authors.initials: KC
authors.lastname: Lee
authors.forename: P J
authors.initials: PJ
authors.lastname: Silver
authors.forename: D C
authors.initials: DC
authors.lastname: Bode
authors.forename: T
authors.initials: T
authors.lastname: Gherezghiher
mesh_terms: D000287:Administration, Topical; D000704:Analysis of Variance; D000818:Animals; D001082:Aqueous Humor / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002415:Cats; D004305:Dose-Response Relationship, Drug; D005123:Eye / Q000098:blood supply / Q000187:drug effects*; D005260:Female; D007429:Intraocular Pressure / Q000187:drug effects*; D008297:Male; D020105:Milrinone; D009883:Ophthalmic Solutions; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D011728:Pyridones / Q000494:pharmacology*; D011817:Rabbits; D012025:Reflex, Pupillary / Q000187:drug effects; D012039:Regional Blood Flow
chemical_list: D009883:Ophthalmic Solutions; D010726:Phosphodiesterase Inhibitors; D011728:Pyridones; D020105:Milrinone