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 studied spectrophotometrically in vitro. The ocular hypotensive effects of the drugs, namely, timolol, befunolol, carteolol, pilocarpine, epinephrine, prostaglandin A2, F2 alpha and E2, also were compared in vivo on eyes of pigmented and albino rabbits. At an initial concentration of 10(-4) M, each of the three beta-blockers exhibited a binding rate of 80-85% as compared to only 40% for pilocarpine and 50% for epinephrine. Almost none of the prostaglandins were found to bind to synthetic melanin. Topically applied, 0.5% timolol and 3% pilocarpine significantly lowered the intraocular pressure in albino but not in pigmented rabbits. Epinephrine (1%) caused a significant reduction in the intraocular pressure both in albino and pigmented rabbits; however, the maximum reduction 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, F2 alpha and E2. These findings show that several ocular hypotensive drugs bind to melanin and suggest that this process can modify the extent of their pharmacological effects when tested in a single dose, or the time-course of their effects when used to treat chronic conditions.
Nagata
A
A
Department of Ophthalmology, Hiroshima University School of Medicine, Japan.
Mishima
H K
HK
Kiuchi
Y
Y
Hirota
A
A
Kurokawa
T
T
Ishibashi
S
S
D000319:Adrenergic beta-Antagonists / Q000378:metabolism / Q000627:therapeutic use; D016115:Albinism, Oculocutaneous / Q000188:drug therapy; D000818:Animals; D004837:Epinephrine / Q000378:metabolism / Q000627:therapeutic use; D005901:Glaucoma / Q000188:drug therapy; D007429:Intraocular Pressure / Q000187:drug effects; D008543:Melanins / Q000378:metabolism*; D015814:Ocular Hypotension / Q000188:drug therapy* / Q000378:metabolism*; D010857:Pigment Epithelium of Eye / Q000187:drug effects*; D010862:Pilocarpine / Q000378:metabolism / Q000627:therapeutic use; D011453:Prostaglandins / Q000378:metabolism / Q000627:therapeutic use; D011817:Rabbits
D000319:Adrenergic beta-Antagonists; D008543:Melanins; D011453:Prostaglandins; D010862:Pilocarpine; D004837:Epinephrine