Ocular actions of an octahydrobenzo[f]quinoline: Ha117.
An octahydrobenzo[f]quinoline compound, Ha117, was examined for activity on: (1) intraocular pressure and in normal, sympathectomized and water loaded rabbits and aqueous flow rate in normal and sympathectomized rabbits, respectively; (2) contractions of the cat nictitating membrane elicited by electrical stimulation of cervical sympathetic nerves; (3) cAMP accumulation in the isolated rabbit iris root-ciliary body preparation. Ha117 lowered intraocular pressure and aqueous flow rate in normal but not in sympathectomized rabbits. Elevated intraocular pressure produced by water loading was suppressed by Ha117 and pretreatment with metoclopramide antagonized the inhibitory effect of Ha117. Neuronally mediated contractions of the nictitating membrane were inhibited in a dose-related fashion by Ha117, and inhibitory effects were antagonized 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 rabbit and cat models suggest that the ocular hypotensive effect of Ha117 is 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 postjunctional suppression of cAMP accumulation.
Potter
D E
DE
Department of Pharmacology and Toxicology, Morehouse School of Medicine, Atlanta, GA 30310-1495.
Ogidigben
M J
MJ
Heath
A R
AR
D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism; D002415:Cats; D002924:Ciliary Body / Q000187:drug effects / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D004294:Domperidone / Q000494:pharmacology; D015259:Dopamine Agents / Q000494:pharmacology*; D004558:Electric Stimulation; D005123:Eye / Q000187:drug effects*; D005260:Female; D066298:In Vitro Techniques; D007429:Intraocular Pressure / Q000187:drug effects; D007498:Iris / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008787:Metoclopramide / Q000494:pharmacology; D009541:Nictitating Membrane / Q000187:drug effects; D011804:Quinolines / Q000494:pharmacology*; D011817:Rabbits; D017448:Receptors, Dopamine D2 / Q000187:drug effects; D013562:Sympathectomy; D013564:Sympathetic Nervous System / Q000187:drug effects
D015259:Dopamine Agents; D011804:Quinolines; D017448:Receptors, Dopamine D2; D004294:Domperidone; C041539:Ha 117; D000242:Cyclic AMP; D008787:Metoclopramide