OCULAR ACTIONS OF AN OCTAHYDROBENZO[F]QUINOLINE - HA117

An octahydrobenzo[f]quinoline compound, Ha117, was examined for activi ty on: (1) intraocular pressure and in normal, sympathectomized and wa ter loaded rabbits and aqueous flow rate in normal and sympathectomize d rabbits, respectively; (2) contractions of the cat nictitating membr ane elicited by electrical stimulation of cervical sympathetic nerves; (3) cAMP accumulation in the isolated rabbit iris root-ciliary body p reparation. Ha117 lowered intraocular pressure and aqueous flow rate i n normal but not in sympathectomized rabbits. Elevated intraocular pre ssure produced by water loading was suppressed by Ha117 and pretreatme nt with metoclopramide antagonized the inhibitory effect of Ha117. Neu ronally mediated contractions of the nictitating membrane were inhibit ed in a dose-related fashion by Ha117, and inhibitory effects were ant agonized by domperidone. Ha117 and an analog, Ha118, did not suppress isoproterenol- and vasoactive intestinal peptide-induced accumulation of cAMP in the rabbit iris root/ciliary body. In vivo results in rabbi t and cat models suggest that the ocular hypotensive effect of Ha117 i s mediated by an action on prejunctional dopamine (DA2) receptors. In vitro data in the rabbit iris root/ciliary body suggest that Ha117 and Ha118-induced lowering of intraocular pressure does not involve postj unctional suppression of cAMP accumulation.