Pilocarpine-induced subsensitivity to carbachol and pilocarpine of ciliary muscle in vervet and cynomolgus monkeys.

Vervet monkeys were given unilateral treatment for two weeks with one 2% pilocarpine eye drop three times daily between 8 a.m. and 6 p.m. (night interval 14h) and were then subjected to anterior chamber perfusion 20 mug pilocarpine intracamerally caused similar and substantial increases in outflow facility in both eyes. Cynomolgus monkeys were unilaterally treated with continuous release of 33 mug/h of pilocarpine for 5-6 days. The facility response to 1 mg/kg pilocarpine iv was small or absent on the treated side. Iridectomized cynomolgus monkeys responded with 12.6+/-5.2 (SD) diopters accommodation to 1.5 mg/kg pilocarpine im, with very similar responses in the two eyes. During continuous release of 30 mug/h pilocarpine, accommodation of the treated eye dropped grdually and after 4-8 days treatment the accommodative response was markedly reduced to pilocarpine 1.5 mg/kg im or 100 mug topically. The degree of subsensitivity was much less when tested with either systemic or topical carbachol. This was also the case in a few vervet experiments. Recovery of full pilocarpine sensitivity took several weeks in the cynomolgus monkey. As an explanation for the excessive subsensitivity and large interindividual differences found with pilocarpine, an individually variable, nonmuscarinic relaxant action counteracting the muscarinic excitatory action is suggested. Clinical implications of this hypothesis are discussed.