On the topically effective ocular hypotensive properties of ICI 147,798, a natriuretic beta-adrenoceptor antagonist, in rabbits.
The ocular antihypertensive effects of ICI 147,798, a natriuretic, non-selective beta-blocker lacking local anaesthetic and intrinsic sympathomimetic activities, were evaluated in unanaesthetized rabbits with water-load-induced ocular hypertension. The racemate was approximately 20 times more potent as a beta-blocker than its d-isomer. The magnitude of reductions in intraocular pressure (IOP) elicited by both compounds was equal following topical administration of an equal dose-concentration (100-300 microliters, 0.5% or 0.75%) to one or both eyes, and the activities were similar to those obtained with timolol. A five-hour duration of the IOP lowering effect was achieved by ICI 147,798 and timolol in this rabbit model. ICI d-147,798 exhibited a shorter duration, which could be prolonged by increasing the concentration of the ophthalmic solution. Timolol caused a pronounced reduction of isoproterenol-induced tachycardia after a single dose (200 microliters, 0.5%) or by repeating the dose twice a day for four consecutive days. Following the same dose regimen, neither ICI 147,798 nor its d-isomer significantly altered the heart rate response produced by isoproterenol. These findings indicate that ICI 147,798, while effective as a potential antiglaucoma agent, does not display the characteristics of beta-blockers on heart rate effects noted with timolol. The results also cast some doubt on the contention that the IOP lowering effect of certain beta-blockers is predominantly determined by specific blockade of beta-adrenoceptors.
Kau
S T
ST
Department of Pharmacology, ICI Pharmaceuticals Group, ICI Americas Inc., Wilmington, Delaware 19897.
Limp
G L
GL
D000287:Administration, Topical; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D007429:Intraocular Pressure / Q000187:drug effects*; D045283:Natriuretic Agents / Q000494:pharmacology*; D011719:Pyrazines / Q000008:administration & dosage / Q000494:pharmacology*; D011817:Rabbits
D000319:Adrenergic beta-Antagonists; D045283:Natriuretic Agents; D011719:Pyrazines; C053707:ICI 147798