Lisuride acts at multiple sites to induce ocular hypotension and mydriasis.
Topically unilaterally applied lisuride caused dose-related lowering of intraocular pressure in ipsilateral (treated) but not in contralateral eyes of normal rabbits. The ocular hypotensive response induced by lisuride was antagonized by pretreatment with metoclopramide, a dopamine receptor antagonist, and was partially reduced by local sympathetic denervation. In contrast to the unilateral effect on intraocular pressure, lisuride caused mydriasis in both eyes. Mydriasis was of greater magnitude and more sustained in normal eyes compared to sympathetically denervated eyes. Additional in vivo experiments demonstrated that lisuride caused dose-related suppression of neuronally initiated contractions of cat nictitating membrane. In in vitro experiments lisuride caused dose-related inhibition of norepinephrine release from isolated rabbit iris-ciliary bodies. Pretreatment with Bay K 8644, a calcium channel activator, did not attenuate lisuride-induced inhibition of norepinephrine release in isolated rabbit iris-ciliary bodies. Because lisuride pretreatment caused no change in isoproterenol-stimulated cAMP accumulation in isolated iris-ciliary bodies, suppression of adenylate cyclase was unlikely. It is concluded that the ocular hypotensive effect of lisuride results, in part, from activation of prejunctional dopaminergic receptors on peripheral sympathetic nerves in the anterior segment of the eye but may also involve antagonism on peripheral postjunctional alpha1 adrenoceptors as well. Bilateral increases in pupil diameter antagonized by metoclopramide suggest a stimulatory action of lisuride on dopamine receptors in the central nervous system.
Potter
D E
DE
Department of Pharmacology and Toxicology, Morehouse School of Medicine, Atlanta, Ga., USA. potter@link.msm.edu
Ogidigben
M J
MJ
Chu
T C
TC
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002415:Cats; D002924:Ciliary Body / Q000187:drug effects / Q000378:metabolism; D018491:Dopamine Agonists / Q000633:toxicity*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D007429:Intraocular Pressure / Q000187:drug effects; D007498:Iris / Q000187:drug effects / Q000378:metabolism; D008090:Lisuride / Q000037:antagonists & inhibitors / Q000633:toxicity*; D008787:Metoclopramide / Q000494:pharmacology*; D015878:Mydriasis / Q000139:chemically induced*; D009541:Nictitating Membrane / Q000187:drug effects; D009638:Norepinephrine / Q000378:metabolism; D015814:Ocular Hypotension / Q000139:chemically induced*; D011680:Pupil / Q000187:drug effects; D011817:Rabbits
D002120:Calcium Channel Agonists; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D008090:Lisuride; D008787:Metoclopramide; D009638:Norepinephrine