Non-additivity of maximal pilocarpine and cytochalasin effects on outflow facility

Living cynomolgus monkeys received intracameral infusions of pilocarpine HCI (P)1 mg ml-1, followed by P + cytochalasin B (CB) 50 microgram ml-1; total outflow facility, measured by two-level constant pressure perfusion, tripled after P alone and then remained stable when CB was added. Other eyes received CB 25 micrograms ml-1 or 50 micrograms ml-1, followed by CB + P1 mg ml-1; facility quadrupled to sextupled after CB, but tended to decrease from those levels, although it remained above baseline, after P was added. The facility decrease accompanying the addition of P after CB might have related to the longer CB exposure, rather than to a specific P effect. These data indicate that despite different mechanisms of action and primary attack points on the outflow apparatus, near- or supramaximal P and CB doses are not additive, and are indeed mutually pre-emptive, in their facility increasing effect. These findings have implications in terms of trabecular-meshwork biophysics, fluid mechanics, and their pharmacological manipulation.