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.
D000818:Animals; D000242:Cyclic AMP / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D004195:Disease Models, Animal; D006439:Hemodynamics / Q000187:drug effects; D007429:Intraocular Pressure / Q000187:drug effects*; D011412:Propanolamines / Q000494:pharmacology*; D011817:Rabbits; D013237:Stereoisomerism; D013997:Time Factors; D013999:Timolol / Q000494:pharmacology*; D014520:Urethane / Q000494:pharmacology; D014869:Water Intoxication / Q000503:physiopathology*
D011412:Propanolamines; D014520:Urethane; D013999:Timolol; D000242:Cyclic AMP