PURPOSE: Pirenzepine is suggested to be a relatively selective muscarinic (M(1)) antagonist and is currently under investigation for the treatment of myopia. Atropine, a nonselective M-type antagonist, is used in the treatment of myopia, but has undesired ocular and systemic side effects. An M(1)-specific antagonist may decrease side effects and remain effective at reducing the progression of myopia. In the current study, the effects of pirenzepine on pupil diameter, resting refraction, and accommodation were studied in rhesus monkeys. METHODS: The time course and extent of mydriasis from subconjunctival injection of 2% pirenzepine were determined in five normal rhesus monkeys, and the effects on static and dynamic accommodation were determined in four rhesus monkeys with permanent indwelling electrodes in the Edinger-Westphal (EW) nucleus of the midbrain. Subconjunctival injections of 0.0002% to 0.2% pirenzepine in log unit dilutions were tested in three monkeys to determine the effects on static EW-stimulated accommodation. At 40 to 50 minutes after pirenzepine injection, accommodation was stimulated pharmacologically in both eyes, and the response was measured for 30 minutes. RESULTS: After 2% pirenzepine injection, pupil size increased 2.02 +/- 0.41 mm, there was a hyperopic shift in resting refraction of 1.07 +/- 0.23 D, and nearly complete cycloplegia occurred. Maximum EW-stimulated accommodation was significantly decreased 20 to 40 minutes after 0.02% or greater pirenzepine. Carbachol-stimulated accommodation was significantly decreased after 0.2% or greater pirenzepine. CONCLUSIONS: Subconjunctival injections of 0.02% or greater pirenzepine result in a significant decrease in accommodation and are probably acting through nonselective muscarinic antagonism. Subconjunctival injections of 0.002% or less pirenzepine do not decrease EW-stimulated accommodation.
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