Cocaine-binding by the pigmented and the nonpigmented iris and its relevance to the mydriatic effect.

Isolated hides from albino and nonalbino guinea pigs were incubated with various concentrations of (±)-">C-cocaine. The nonpigmented iris accumulated little drug, while the pigmented iris accumulated very large amounts. The ratio for the accumulation was 1:18. Drug accumulated by the nonpigmented iris could be easily washed off at a single exponential rate toith tVz of 10 minutes. The drug accumulated by pigmented iris was resistant to ivashing. In the pigmented iris (-)-ephedrine reduced the accumulation of (±)->C-cocaine. The drug is also accumulated by the bovine melanin granules. Chemical sympathectomy toith 6-OH-dopamine or phenoxybenzamine treatment, which drastically reduced the uptake of (-)->C-norepinephrine, failed to reduce the accumulation of (±)->C-cocaine. As compared to the effect in the pigmented iris, nonlabelled cocaine was the more effective inhibitor of (-)->C-norepinephrine uptake in the nonpigmented iris. Melanin pigment appears to be a site of loss for the ocular drugs like cocaine, so that a lesser concentration of the drug is available for the interaction with the adrenergic neurones to produce lesser mydriatic effects in the pigmented iris. In the nonpigmented iris, a majority of the drug will be available for interaction toith the neurons to produce greater mydriatic effects.