DUAL ACTION OF OXYFEDRINE ON CARDIAC CONTRACTILITY

1. Oxyfedrine, at concentrations of 10-7 to 3×10-6 mol/l, increased the force of contraction of the isolated papillary muscle of the guinea pig. It was difficult to abolish this effect by repeated exchange of the bath solution. The maximum inotropic action was about 40% that of noradrenaline. Peripheral catecholamine stores were not involved, neither were the breakdown products of oxyfedrine, norephedrine and 3-methoxyacrylophenone. The latter had positive inotropic actions at 10 times and 100 times higher concentrations, respectively, than the parent substance. Their inotropic effects were caused by the release of endogenous catecholamines. 2. The positive inotropic effect of oxyfedrine was not influenced by burimamide (10-4mol/l). (±)-Propranolol (10-9 and 10-8 mol/l) shifted the concentration-effect curve of oxyfedrine to the right. The inhibition of the inotropic effect by 10-7 mol/l(±)-propranolol was not surmountable. 3. In the presence of 10-6 mol/l propranolol, oxyfedrine had only a concentration-dependent negative inotropic action. This was due mainly to a decrease in contraction velocity and was accompanied by a shortening in the time to peak force. The duration of the transmembrane action potential and the depolarization speed were not reduced (10-5mol/l oxyfedrine). 4. The positive inotropic effect of oxyfedrine was enhanced by the phosphodiesterase inhibitor theophylline (10-4mol/l). The maximum of the concentration-effect curve of oxyfedrine, i.e., the efficacy of this substance, was almost doubled. 5. A quantitative analysis of the interaction of oxyfedrine with the positive inotropic effect of isoprenaline proved that oxyfedrine acted mainly as a partial agonist at cardiac β-adrenoceptors. Its positive inotropic effect due to stimulation of β-adrenoceptors was, to some extent, antagonized by its negative inotropic action. © 1979 Springer-Verlag.