Effect of moxonidine on drug induced cardiac arrhythmias and its possible antinociceptive effect in rats

Moxonidine is a new second generation, centrally acting antihypertensive drug. It causes peripheral sympathoinhibition, triggered at the level of central nervous 11-receptors. The present study was designed to screen various cardiovascular effects of moxonidine both in-vivo and in-vitro as well as to investigate the possible analgesic effect of moxonidine. In-vitro results revealed that moxonidine produced dose related inhibition of the force of contraction of the isolated perfused rabbit's heart. A vagal like action was suggested because both muscarinic and nicotinic receptors antagonist abolished this effect. In vivo results showed that acute intravenous injection of moxonidine significantly reduced heart rate of normotensive rats dose dependantly. Moxonidine in different doses exhibited pronounced antiarrhythmic effects characterized by dose-dependent increase in adrenaline arrhythmogenic dose and significant decrease in the number of extrasystoles. Furthermore, moxonidine in different doses, increased both the arrhythmogenic and ventricular fibrillatory doses of ouabain in a dose-dependent manner. Lastly, acute moxonidine administration was found to provide potent antinociceptive efficacy in control of acute pain in rats and yohimbine, was able to antagonize this effect

Cardioprotective effect of captopril on the catecholamine-induced myocardial necrosis

The cardioprotective effect of captopril, a converting enzyme inhibitor, was studied on the isoprenaline-induced myocardial necrosis [M.N.] in rats. The degree of protection was assessed biochemically by measuring variations in level of serum CPK and histopathologically by estimating infarct size [I.S.]% i.e. surface area of injured myocardium to area of heart sections, after being stained with haematoxylin basic fuchcin picric acid stain. Also, injury currents in ECG were looked for. Pretreatment with captopril in a dose of 100 ug/kg i.p., 15 min. before injection of a necrotizing dose of isoprenaline [300 mg/kg] s.c., was found to be highly protective. The serum CPK and I.S. of rats pretreated with captopril were markedly decreased. Moreover, the injury currents, which were observed in ECG of rats treated with isoprenaline, disappeared in captopril treated rats. Injected 15 min. after isoprenaline, captopril was found to be protective but less effective than if it was administered before isoprenaline although used in the same dose level. The mean values of serum CPK and I.S. of post-treated rats were significantly lower than the corresponding values in isoprenaline-treated rats. Further reduction of the cardioprotective effect of captopril was noticed on increasing the post-treatment interval to 30 min. Captopril protects the heart effectively against catecholamine-induced myocardial necrosis. This protective effect proved to be time-related, the earlier the intervention, the better the results