EFFECTS OF DOPAMINE D-1 AND D-2 RECEPTORS ON INTRAOCULAR-PRESSURE IN CONSCIOUS RABBITS

This investigation was designed as a randomized, placebo-controlled, d ouble-masked, crossover study in NZW rabbits with normal intraocular p ressure (IOP) to investigate dopaminergic effects on IOP. SKF 38393, a selective D1-receptor agonist, increased, and SDZ PSD-958, a selectiv e D1-receptor antagonist, decreased IOP, respectively. The selective D 2-receptor agonist quinpirole decreased IOP, whereas the selective D2 receptor antagonist metoclopramide had no significant effect. Combinat ions of quinpirole with SDZ PSD-958 decreased IOP in an additive manne r. SDZ GLC-756, a mixed D1-receptor antagonist/D2-receptor agonist, de creased IOP in a dose-dependent manner with a maximum effect greater t han the maximum effects produced either by the D1-receptor antagonist SDZ PSD-958 and the D2-receptor agonist quinpirole. The effect of SDZ GLC-756 could only be partially blocked by the selective D2-receptor a ntagonist metoclopramide suggesting that both D1-receptor blockade and D2-receptor stimulation participate in its IOP-lowering effect. Tonog raphy suggests that SDZ GLC-756 has no significant effect on outflow f acility. Furthermore, the results suggest that both D1 and D2 receptor s each play an independent role in the regulation of IOP in rabbits. T hus, simultaneous blockade of D1 receptors and stimulation of D2 recep tors may provide a new pharmacological approach for the treatment of o cular hypertension frequently associated with glaucoma.