The Effect of Cocaine on the Relative Chronotropic Potencies of Sympathomimetics 1

Summary

It is concluded that the relative chronotropic potencies of NE, Epi and Iso are similar to the relative inotropic potencies reported previously. If neuronal uptake is functional the relative potencies are Iso > Epi ≥ NE. When neuronal uptake is excluded as a means of removing agonists from the vicinity of receptors (i.e., in the presence of cocaine) the potencies become Iso ≥ NE > Epi. This change in the order of relative potencies is due to the fact that in the presence of cocaine the ED₅₀ values of NE and Epi are reduced while the ED₅₀ of Iso remains the same. The order of potency of these three adrenergic agonists is not changed by endogenous norepinephrine depletion induced by reserpine. The sensitization of atria to NE and Epi by cocaine is, however, substantially greater after reserpine.