The rate of action of cholinergic drugs in guinea-pig isolated atria

Abstract

1)The rate at which the negative inotropic effect occurs was studied for several parasympathomimetic drugs in isolated, electrically driven atria of guinea-pigs. The time course of each effect could be described by an exponential function. The rates determined for different drugs displayed noticeable differences. The highest rate was established for acetylcholine, the lowest rate for norarecoline. 2) For each drug the rate of the effects was dose dependent. The relationship between the rate of the effects and the applied concentrations obeyed a hyperbolic function. 3) A hyperbolic function of this kind should be expected, if the formation of the drug receptor complexes governs the rate of the effect. 4) Evaluating the hyperbolic function, the dissociation constant ( K) of the drug receptor complex and the rate constants for the association ( k 12) and the dissociatiion ( k 21) of the drug receptor interaction could be estimated for each drug. 5) The dissociation constants obtained by kinetic analysis agree satisfactorily with the ED 50 value calculated from conventional dose response curves. The order of the association rate constants of the drugs investigated runs inversely proportional to the corresponding ED 50 values. On the other hand the dissociation rate constants show the same order as the rates of the negative inotropic effects of the different cholinergic drugs.