Effect of proxodolol and other adrenoblocking agents on the pharmacological properties of clophelin

Abstract

Proxodolol is a new Russian [3,ct-adrenoblocking drug possessing antihypertensive, antiischemic, and antiglaucomatosis properties [1 -4]. This drug is already used in practical ophthalmology for reducing the intraocular pressure in patients diagnosed with glaucoma.The complex chemotherapy of glaucoma involves, in addition to [3-adrenoblocking agents and pilocarpin, the administration of elophelin (clonidine). Because this drug has a high criminogenic potential, it was of interest to study the effect of proxodolol and some other adrenoblocking agents on the main pharmacological manifestations of clophelin. METHODSa) Effect of drugs on the body temperature and the course of cerebral ischemia. Experiments were performed on a group of 209mice (CBA. C57B1)F1 weighing 19-27 g. The body temperature of mice was measured at a depth of 3.5 cm with a TPEM-1 electric thermometer. The drug effects were studied on a decapitation model of total cerebral ischemia and involved determination of the duration of agonal breathing. Clophelin was introduced 30 min before decapitation at a dose of 1 mg/ kg (s.c.), and adrenoblocking drugs were injected 45 rain before decapitation: proxodolol and labetalol (30 mg/kg, s.c.), propranolol (10 mg/kg, s.c.), b) Sedative effect. Experiments were performed on a group of 144male mongrel mice weighing 18-20 g. The spontaneous motor activity was determined using an OptoVarimex instrument (Italy) every 10 rain during a time period of 60 min. Clophelin at a dose of (0.5 mg/kg, i.p.) and proxodolol (2 mg/kg, i.p.) were introduced either separately or in combination (a new ophthalmic medication form); timolol at a dose of 2 mg/kg (i.p.) was also injected either either separately or in a combination with clophelin (0.5 mg/kg, i.p.). c) Effect on the coordination of movements. Experiments were performed on 30 male mice weighing 18-20 g divided into groups of 5 animals. The manifestations of motor disorder were evaluated using the "rotating rod" test. Each group was placed on the testing device (Ugo-Basile, Italy), and the number of mice incapable of staying on the rotating rod was counted. The animals were injected intraperitoneally with solvent (0.1 ml of 0.9 % sodium chloride), proxodolol (2 mg / kg), clophelin (0.5 or 1 mg / kg), or a combination of the two drugs (a new ophthalmic medication form) at a dose of 0.5 or I mg/kg, as calculated for clophelin. d) Hypotensive action. Experiments were performed on a group of 4 rabbits weighing 2.5 -4 kg narcotized with urethane (1.2 g/kg, i.v.). The arterial pressure in a common carotid artery was measured with a mercury manometer and recorded on a smoked tape of kymograph. Clophelin was in-0091 -150X/97/3104--0163518.00 9 1997 Plenum PuNishing Corporation