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Effects of D-timolol on intraocular pressure (IOP), beta blocking activity, and the dynamic changes of drug concentrations in aqueous humor.

L-timolol has been used successfully in the treatment of glaucoma. Because of its powerful beta blocking activity, however, more and more side effects have been reported. D-timolol, an optic isomer of L-timolol with much less beta blocking activity, was noted to have similar ocular hypotensive effects through inhibition of aqueous production as L-timolol. Thus, it is expected that D-timolol may reduce the side effects considerably if it is used in the clinics. In this study, we observed the ocular hypotensive effect of 0.5% D-timolol in normotensive and water-loaded rabbits as well as in patients with glaucoma or ocular hypertension. A significant reduction of intraocular pressure (IOP) which lasted at least six hours was observed. No side effects, either locally or systemically, were found. The concentration of D-timolol was traced in rabbits' aqueous humor after topical administration. The drug quickly appeared in the aqueous 30 minutes after instillation of 100 microliters 1% D-timolol. The peak concentration was 1916.5 ng/ml. It declined to a minimum in four hours, although the hypotensive effect could last at least six hours. For estimating the beta blocking potency of D-timolol, radioligand binding assay was employed to calculate the Ki value from isolated cell membrane of rabbits' lung. It showed that the beta blocking potency of D-timolol was much less than that obtained from L-timolol. It is concluded that D-timolol may be a valuable antiglaucoma agent comparable to L-timolol in lowering the IOP. The side effects induced by beta blocking agents we are using currently might be considerably reduced with D-timolol.