Abstract
Abstract: :
Purpose: Pirenzepine is undergoing FDA clinical trials for the treatment of myopia. It has been suggested that at appropriate concentrations, pirenzepine may be a relatively selective muscarinic type 1 antagonist with fewer ocular side effects than a non–selective antagonist such as atropine. Previously we found that subconjunctival injection of 2% pirenzepine caused complete cycloplegia in rhesus monkeys. In this study, lower concentrations of pirenzepine were tested to determine the effects on accommodative amplitude. Methods: Accommodation experiments were performed on three rhesus monkeys with permanent indwelling electrodes in the Edinger–Westphal nucleus of the midbrain. Accommodation was tested with five concentrations of pirenzepine, 2%–0.0002% in log unit dilutions. An accommodative stimulus–response function was measured with a Hartinger coincidence refractometer in both eyes before and 45 minutes after subconjunctival injection of 0.2 ml pirenzepine into one eye. The response to a current amplitude that produced maximum accommodation was measured for 40 minutes following pirenzepine injection. Accommodation was also stimulated pharmacologically in both eyes 50 minutes after pirenzepine injection. Results: Pirenzepine concentrations of 0.02% or greater resulted in a significant decrease in maximum centrally stimulated accommodation, with decreases of 11.6 ± 0.96 D following 2% (p<0.05), 9.9 ± 1.7 D following 0.2% (p<0.05) and 3.2 ± 1.1 D following 0.02% (p<0.05). Centrally stimulated accommodation was significantly reduced in the control eye following injection of 2% pirenzepine in the treated eye, but not for any of the lower concentrations. Carbachol stimulated accommodation was significantly decreased following injection of pirenzepine concentrations of 0.2% or greater compared to the control eye. Conclusions: Subconjunctival injection of pirenzepine at concentrations of 0.002% or less did not significantly decrease centrally or pharmacologically stimulated accommodation in rhesus monkeys. These results suggest that pirenzepine concentrations of 0.02% or greater result in non–selective muscarinic antagonism, while concentrations of 0.002% or less may maintain M1 selectivity.
Keywords: ciliary muscle • myopia • pharmacology