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Abstract
Three soft drug analogs of atropine have been tested for mydriatic activity in rabbits' eyes and their in vitro metabolic pathway has been investigated in rat, rabbit and human blood. The three soft drugs were found to produce an equieffective mydriatic activity to atropine and tropicamide. At equieffective concentrations, their durations were shorter with AUC's 12–21% that of 0.25% atropine and 44–80% that of 0.2% tropicamide. The untreated control eyes were observed to dilate after unilateral ocular administration of atropine, but not with unilateral soft drug treatment. In vitro stability studies showed that the soft ethyl analog was less stable in rat blood and rat liver homogenate than in rabbit or human blood. The metabolic product of the soft ethyl derivative in biological media was proven to be the corresponding inactive acidic metabolite predicted by the soft drug design. The ultrashort durations and the potentially nontoxic systemic properties of the soft mydriatics offer promise for use in ophthalmoscopy and in other ocular procedures where a short acting anticholinergic type of mydriatic would be indicated.