Effects of l- and d-timolol on cyclic AMP synthesis and intraocular pressure in water-loaded, albino and pigmented rabbits.

Topical 2% l- or d-timolol reduced the elevation of intraocular pressure induced by water-loading in conscious rabbits. This drug effect appeared on the peak elevation (in pigmented eyes) and on the down-phase (in albino and pigmented eyes) of elevated intraocular pressure. The contralateral eye and the treated eye responded similarly. In urethane anesthetized, water-loaded rabbits, a greater inhibitory effect of l-timolol was observed in pigmented eyes than in albino eyes. Two per cent l-timolol caused alterations of heart rate and arterial blood pressure in water-loaded anesthetized rabbits, but time courses of these alterations did not correlate with the inhibitory effect on the elevation of intraocular pressure. The beta-adrenergic antagonistic activity of l-timolol and d-timolol were compared by their ability to inhibit l-isoproterenol-stimulated cyclic AMP synthesis in the rabbit iris-ciliary body preparation in vitro. The I50S for l- and d-timolol differ by about 1.5 log units. In our studies, d-timolol has little of the intraocular pressure lowering and the beta-adrenergic antagonistic activity of l-timolol. Thus, the conscious, water-loaded, pigmented rabbit can be used as a model for studying the effects of beta-adrenergic antagonists on intraocular pressure.