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  • Title: Pharmacological effects of topical timolol in the rabbit eye.
    Author: Bartels SP, Roth HO, Jumblatt MM, Neufeld AH.
    Journal: Invest Ophthalmol Vis Sci; 1980 Oct; 19(10):1189-97. PubMed ID: 6106643.
    Abstract:
    The ability of timolol to act as a beta-adrenergic antagonist in the cornea and in the iris--ciliary body of albino rabbits is reported. In vitro, timolol potently blocks the isoproterenol-stimulated synthesis of cAMP. In the iris-ciliary body, the apparent inhibition constant (K1) for timolol is 0.6 nM, indicating that timolol is approximately seven times more potent than propranolol. Topical timolol (0.5% and 4%) rapidly inhibits the beta-adrenergic--stimulated synthesis of cAMP in both corneal and iris--ciliary body tissues. Within 3 hr, however, the iris--ciliary body tissue regains its ability to produce large amounts of cAMP when challenged in vitro with isoproterenol. The washout of timolol from corneal tissue is more protracted. Intraocular pressure measurements by anterior chamber cannulation of anesthetized rabbits indicate that topical timolol (0.5% and 4%) has no significant influence on intraocular pressure. These concentrations of timolol significantly decrease heart rate but do not affect femoral arterial blood pressure. Because of the marked potency of timolol clinically, we conclude that the effects of the drug in the rabbit do not completely account for its therapeutic efficacy in humans, which must depend on more complex pharmacological actions.
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