The nature of the antagonism by methoxamine of the chronotropic and inotropic effects of catecholamines

Summary

Chronotropic and inotropic concentration-effect curves were determined concurrently with a preparation consisting of the right atrium of a guinea-pig, beating spontaneously, and a strip of the left atrium driven at a constant frequency. In concentrations below 10⁻⁴, M, methoxamine usually had no effect upon the strength or frequency of contraction; at higher concentrations it depressed both. Methoxamine produces an approximately parallel shift in the log concentration-effect curves for l-isoproterenol, l-norepinephrine, and l-epinephrine, the chronotropic and inotropic curves being shifted about equally. A substantial shift is produced by concentrations of methoxamine that have no inotropic or chronotropic actions themselves. The positive chronotropic effect of histamine is not influenced by methoxamine. The evidence obtained is consistent with the hypothesis that the methoxamine-isoproterenol antagonism is a simple competitive one with a pA₂ of 5.2. The methoxamine-epinephrine antagonism is more complicated, possibly partly as a result of a depressant effect of epinephrine itself in high concentrations.