BINDING OF ANTIGLAUCOMATOUS DRUGS TO SYNTHETIC MELANIN AND THEIR HYPOTENSIVE EFFECTS ON PIGMENTED AND NONPIGMENTED RABBIT EYES

The binding of ocular hypotensive drugs to synthetic melanin was studi ed spectrophotometricatly in vitro. The ocular hypotensive effects of the drugs, namely, timolol, befunolol, carteolol, pilocarpine, epineph rine, prostaglandin A2, F2alpha and E2, also were compared in vivo on eyes of pigmented and albino rabbits. At an initial concentration of 1 0(-4) M, each of the three beta-blockers exhibited a binding rate of 8 0-85% as compared to only 40% for pilocarpine and 50% for epinephrine. Almost none of the prostaglandins were found to bind to synthetic mel anin. Topically applied, 0.5% timolol and 3% pilocarpine significantly lowered the intraocular pressure in albino but not in pigmented rabbi ts. Epinephrine (1%) caused a significant reduction in the intraocular pressure both in albino and pigmented rabbits; however, the maximum r eduction was greater in albino than in pigmented rabbits. Intraocular pressure was reduced to the same extent and with a similar time-course in both albino and pigmented rabbits by 0.02% prostaglandin A2, F2alp ha and E2. These findings show that several ocular hypotensive drugs b ind to melanin and suggest that this process can modify the extent of their pharmacological effects when tested in a single dose, or the tim e-course of their effects when used to treat chronic conditions.