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  • Title: Pharmacological studies of mabuterol, a new selective beta 2-stimulant. II: Effects on the cardiovascular system and smooth muscle organs.
    Author: Osada E, Murai T, Ishizaka Y, Sanai K.
    Journal: Arzneimittelforschung; 1984; 34(11A):1641-51. PubMed ID: 6152157.
    Abstract:
    Effects of dl-1-(4-amino-3-chloro-5-trifluorome-thyl-phenyl)-2-tert.-bu tylamino-ethanol hydrochloride (mabuterol) on the cardiovascular system and smooth muscle organs were investigated in comparison with those of isoprenaline (isoproterenol), salbutamol and procaterol, and the following results were obtained. Mabuterol (i.v.) produced a dose-dependent decrease in the blood pressure at doses ranging from 0.3-1000 micrograms/kg, and the heart rate was slightly increased at 0.3-30 micrograms/kg but decreased at 100-1000 micrograms/kg in rats, cats and dogs. The effects of mabuterol on the blood pressure, total peripheral vascular resistance (TPR) and heart rate were respectively 14, 37 and 104 times less potent than those of isoprenaline and there were none on the maximum dp/dt in the left ventricle in cats. In dogs, mabuterol had 356 and 118 times less effect on the blood pressure and TPR than isoprenaline and slightly increased the heart rate and maximum dp/dt. Mabuterol (p.o.) decreased the blood pressure at doses ranging from 3 micrograms-100 mg/kg, and the heart rate was increased at 3 micrograms-10 mg/kg, but decreased at 100 mg/kg in conscious and anesthetized rats. In the guinea pig atria, mabuterol slightly increased the heart rate and contractile force, but in the electrically driven left atrium mabuterol had no effect whereas procaterol slightly increased the contractile force. Mabuterol inhibited the positive inotropic effect of isoprenaline at 10(-7) g/ml and decreased the maximum driving frequency at 3 X 10(-6) g/ml. Mabuterol was 3 times more potent in relaxing the isolated rat uterus, but 700 times less potent than isoprenaline in relaxing the rabbit jejunum. Mabuterol (p.o.) depressed the intestinal propulsion and was equipotent to isoprenaline and 2.5 times less potent than salbutamol. Mabuterol had no effect on alpha-adrenergic, acetylcholine and histamine receptors. These results suggest that mabuterol has a specific effect on beta 2-adrenoceptors with no beta 1-stimulation. In addition, mabuterol exhibited beta 1-blocking activity at dosages 200-300 times higher.
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