AGN 191976: a novel thromboxane A2-mimetic with ocular hypotensive properties

Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics
A H KraussR M Burk

Abstract

The possible subdivision of thromboxane A2-sensitive (TP) receptors is currently a controversial subject. We report herein on a novel thromboxane A2 mimetic, AGN 191976, which has almost identical pharmacological activity to the well-characterized prostaglandin H2/thromboxane A2 (PGH2/TxA2) mimetic U-46619, but its effects on intraocular pressure are quite distinct from U-46619. Prostanoid receptor activity was determined in vitro using different smooth muscle assays and platelets. Intraocular pressure was measured tonometrically in ocular normotensive Beagle dogs and Cynomolgus monkeys. Conjunctival microvascular permeability was determined in guinea pigs. Despite closely resembling U-46619 as a potent and selective TP receptor agonist, AGN 191976 was a potent ocular hypotensive in dogs and monkeys whereas U-46619 did not lower IOP in either species. The ocular hypotensive effect of AGN 191976 in dogs was attenuated by pretreatment with the TP receptor antagonist SQ 29548. Thus, the ocular hypotensive effects of AGN 191976 are consistent with TP receptor stimulation. Both TxA2-mimetics caused plasma leakage in the guinea pig conjunctiva. The disparate activities of U-46619 and AGN 191976 in our studies suggest the existence of...Continue Reading

References


❮ Previous
Next ❯

Citations

May 11, 2002·Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics·N A SharifS X Xu
Aug 1, 1997·Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics·A H KraussJ Senior
Jan 1, 2008·Expert Review of Ophthalmology·Zhou WanW Daniel Stamer
Apr 14, 2016·Ophthalmic Genetics·Lance P Doucette, Michael A Walter

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antihypertensive Agents: Mechanisms of Action

Antihypertensive drugs are used to treat hypertension (high blood pressure) which aims to prevent the complications of high blood pressure, such as stroke and myocardial infarction. Discover the latest research on antihypertensive drugs and their mechanism of action here.

Related Papers

Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics
A H KraussJ Senior
Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics
B'Ann T GabeltPaul L Kaufman
© 2021 Meta ULC. All rights reserved