title: Binding of timolol to iris-ciliary body and melanin: an in vitro model for assessing the kinetics and efficacy of long-acting antiglaucoma drugs.
abstract: Topical beta blockers are used to treat glaucoma patients. These drugs inhibit aqueous production for prolonged periods of time. The purpose of this study was to determine whether timolol maleate (a non-specific beta blocker) binds to human iris-ciliary body (CB) melanin and to elucidate the binding characteristics of the drug to melanin. Timolol bound to bovine iris and ciliary body by two possible mechanisms. The binding kinetics indicate that the binding is probably of a nonspecific nature. There was no statistically significant differences between the melanotic tissues (CB, iris) and the nonmelanotic tissues (lens, cornea, liver, kidney) regarding the amount of timolol bound. However significantly more timolol was bound to the isolated melanins than the whole tissues. Timolol was released from the nonmelanotic tissues at a much faster rate than from the melanotic tissues. The amount of timolol bound to iris-CB from albino and pigmented rabbits showed that the amount of timolol bound to these tissues diminished in the following order: black or gray greater than brown greater than albino. It was also found that the rate of timolol release decreased in the following order: albino greater than gray greater than brown or black. Our results demonstrate the binding of beta blocker to human, bovine and rabbit iris-CB and consequent slow release of timolol from these tissues.
authors.affiliation: Department of Ophthalmology, University of Toronto, Canada.
authors.forename: I A
authors.initials: IA
authors.lastname: Menon
authors.forename: G E
authors.initials: GE
authors.lastname: Trope
authors.forename: P K
authors.initials: PK
authors.lastname: Basu
authors.forename: D C
authors.initials: DC
authors.lastname: Wakeham
authors.forename: S D
authors.initials: SD
authors.lastname: Persad
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D002924:Ciliary Body / Q000378:metabolism*; D006801:Humans; D007498:Iris / Q000378:metabolism*; D007700:Kinetics; D008543:Melanins / Q000378:metabolism*; D010858:Pigmentation; D013999:Timolol / Q000378:metabolism* / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D000319:Adrenergic beta-Antagonists; D008543:Melanins; D013999:Timolol