Abstract
A direct effect of methoxamine on the contractile state of heart muscle was determined by examining its effects on isometric peak force (F), maximum velocity of force development (dF/dt) and time to peak force (TPF) in isolated canine trabeculae. Methoxamine at the concentrations over 5×10-5M caused a concentration-dependent depression of F and dF/dt. TPF was slightly shortened at higher concentrations of methoxamine (over 1×10-4M). These results suggest that methoxamine possesses a direct negative inotropic action which is mainly due to a decrease in the intensity of the active state. An increase in F produced by isoproterenol was antagonized by methoxamine at a concentration about 100 times higher than that of isoproterenol, suggesting a weak beta-adrenergic blocking action of methoxamine. This antagonistic action of methoxamine was seen also in the effects of isoproterenol on dF/dt as well as TPF. The effect of methoxamine on the mechanics of muscle contraction is qualitatively similar to, but quantitatively different from that of other beta-adrenergic blockers.
