Ocular inhibitory effects of the dopamine DA2 agonist (Ha-118) in cats and rabbits

1. Topical administration of the dopamine (DA2) receptor agonist, Ha-118, produced unilateral ocular hypotension and miosis in normal cats. 2. The ocular hypotensive and mitotic effects of Ha-118 were not observed in surgically sympathectomized cats indicating that an intact sympathetic pathway is necessary to demonstrate activity. 3. Ha-118 caused dose-dependent suppression of contractions of the cat nictitating membrane (CNM) elicited by electrical stimulation of the pre- and postganglionic sympathetic nerve trunks but not by exogenously administered noradrenaline suggesting that Ha-118 affected prejunctional but not ganglionic or postjunctional receptors. 4. Sulpiride antagonized Ha-118-induced inhibition of neuronally mediated contractions in the CNM suggesting an interaction at DA2 receptors. 5. Topical administration of Ha-118 inhibited the rise in intraocular pressure induced by oral water loading in rabbits. 6. Topical pretreatment with metoclopramide, a DA2 antagonist, inhibited the ocular antihypertensive effect of Ha-118 in rabbits. 7. These studies demonstrate that Ha-118 decreased intraocular pressure (IOP) and pupil diameter (PD) in the cat and that this activity can be correlated with suppression of peripheral sympathetic tone in the CNM.