ICI 118,551: an effective ocular hypotensive agent with selectivity for the ciliary process beta 2-adrenoceptor and with minimal cardiac side effects

British Journal of Pharmacology
J A Nathanson

Abstract

Prior biochemical studies have shown that the ciliary process epithelium, which is involved in the secretion of aqueous humour, is rich in beta-adrenoceptors with pharmacological characteristics similar to those of the beta 2 subclass. The present experiments demonstrate that the beta-adrenoceptor antagonist, ICI 118,551, is a potent inhibitor of isoprenaline-stimulated adenylate cyclase activity measured in broken cell preparations of rabbit ciliary process. In rabbit cardiac muscle, however, ICI 118,551 is a relatively weak antagonist of isoprenaline-stimulated adenylate cyclase, being approximately 100 fold less potent than the non-selective beta-adrenoceptor antagonist, timolol. ICI 118,551 is also less potent than timolol in inhibiting isoprenaline-sensitive adenylate cyclase of rabbit lung. ICI 118,551 applied topically to eyes of unanaesthetized rabbits causes a dose-dependent decrease in intraocular pressure. Furthermore, in a blind crossover study in rabbits, topically applied ICI 118,551 decreased intraocular pressure for more than 6 h and was more effective than an identical dose of the clinically effective anti-glaucoma agent, timolol. Systemic absorption from topically-applied timolol, but not ICI 118,551, is suffi...Continue Reading

References

Jul 1, 1977·British Journal of Pharmacology·J L ImbsC G Wermuth
May 1, 1979·Survey of Ophthalmology·T J Zimmerman, W P Boger
Apr 1, 1981·The Journal of Pharmacy and Pharmacology·S R O'Donnell, K Walduck
May 1, 1981·British Journal of Pharmacology·J A Nathanson
Dec 1, 1980·Proceedings of the National Academy of Sciences of the United States of America·J A Nathanson
Dec 1, 1982·The British Journal of Ophthalmology·G E Trope, B Clark

Related Concepts

ICI 118551, hydrochloride
Adenylyl Cyclase Inhibitors
Adrenergic beta-Antagonists
Metazoa
Antihypertensive Agents
Ciliary Body
Pulse Rate
Physiologic Intraocular Pressure
Novodrin
Lung

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