Ocular hypotensive effect of 7 series of newly synthetised adrenoreceptor blockers: 3-[4-[3-[4-aryl-1-piperazinyl]-isopropanoloxy]phenyl]- 4[3H] quinazolones in rabbits

ABSTRACT

Screening of an ocular hypotensive effect of seven newly synthesized B-blockers was performed. Aqueous solutions of the hydrochloride salts of the drugs, given the code 3a, b, c, d, f, g were applied locally [50 ug/0.25 ml] or administered intravenously through the marginal vein [1 mg/kg] in groups of adult healthy male rabbits, each of 6 animals. Controls used were saline solutions having the same pH as that of the drugs. The intraocular pressure [IOP] was measured using weighted Schiotz tonometer at different time intervals ranging from 15-405 minutes after the drug administration, and compared with controls. The intravenous administration of all drugs tested induced hypotensive action. The onset of action appeared after 45, 60, 45, 30, 75, 15 and 75 minutes, while the duration of action lasted for 150, 310, 210, 120, 90, 60 and 105 minutes respectively. The peak of ocular hypotensive effect of these drugs were obtained after 75, 150, 105, 45, 75, 30 and 75 minutes and amounted to 24.9%, 37.4%, 40.6%, 24.5%, 24.5%, 24.6% and 20.7% respectively. On the other hand, the topical application of drugs, 3 a, b, c, d, e, g, induced an ocular hypotensive action. Its onset appeared after 75, 60, 75, 120, 90 and 75 minutes. While, their duration of action was 165, 300, 270, 135, 240 and 165 minutes respectively. Time peak of ocular hypotensive effect of these drugs were obtained after 120, 240, 180, 120, 150 and 120 minutes respectively and amounted to 42,7, 33.9, 38.6, 25, 27.9 and 21.2% respectively. Screening of these drugs point to a probable useful ocular hypotensive agents which needs further clinical studies