The experiments were designed to study the well-known pigment-dependent
mydriatic effect of
atropine in the eye. In vitro, relative to the accumulation of 3H-atropine by the nonpigmented rabbit iris, the pigmented iris accumulated high amounts of the
drug. A nonpigmented tissue, stomch fundus strip, obtained from either albino or nonalbino animals, accumulated relatively low amounts of 3H-atropine. On repeated washings, the accumulated
drug from the nonpigmented tissues was rapidly lost, T 1/2 of 14 minutes, while that accumulated by the pigmented iris was retained much longer. Although in vitro aqueous humor from serum-
atropinesterase positive rabbits rapidly degraded
atropine, extracts from irides of the same type of rabbit gave a single peak radioactivity, with Rf identical to the authentic
atropine sulfate. The accumulation of 3H-atropine by pigmented human iris or pigment epithelium was similar to that observed for the pigmented rabbit iris. pA2 values of
atropine from nonpigmented iris and from fundus strips varied between 8.58 and 8.88 with slope values close to 1. The pA2 value of
atropine in pigmented iris was 8.82; at higher concentrations,
atropine was less effective compared to the nonpigmented iris. In the pigmented iris, the lesser effectiveness of the
drug at high concentration could be explained on the basis of accumulation of the
drug by the pigment cell and its constituents. Thus, the free concentration of the
drug in the vicinity of the
muscarinic receptor will fall. The lesser concentration will give weaker
muscarinic blockade in the pigmented iris. On repeated washing, the
atropine blockade of the nonpigmented iris could be easily washed out while that in the pigmented iris was retained. In vivo, the relative T 1/2 for the duration of
atropine mydriasis in rabbits were: albino
atropinesterase-positive, 3.8 hours; nonalbino
atropinesterase-positive, 12.4 hours; albino
atropinesterase-negative is greater than or equal to 96 hours. Only the latter T 1/2 for the duration of
atropine mydriasis is quite clear. The small magnitude of the
mydriatic effect in humans is explained by the loss of free
drug to the pigment cells and their constituents. The longer duration of
mydriatic effect in the heavily pigmented eye is explained on the basis of slow release of the accumulated
drug onto the
muscarinic receptor.