Abstract

On spontaneously beating isolated guineapig atria cocaine has both rate-increasing and rate-decreasing effects. The former effects are due both to the release of endogenous norepinephrine and to the increase in sensitivity to norepinephrine. In addition, cocaine has a direct decelerating effect on the atrial pacemaker, which is unmasked in atria pretreated with reserpine or exposed to propranolol (or both). The negative chronotropic effect of cocaine appears to differ from that of another decelerating agent, veratramine, since cocaine fails to antagonize maximal effects of either norepinephrine or histamine. The norepinephrine-releasing effect of cocaine is increased by pretreatment with the monoamine oxidase inhibitor, pargyline, and decreased at lower temperatures. The negative chronotropic effect of cocaine is unaffected by pretreatment with pargyline and reduced at lowered temperatures. The cocaine-induced supersensitivity to norepinephrine is affected neither by pretreatment with pargyline nor by a decrease in temperature, although atria at 27°C are much more sensitive to norepinephrine than at 37°C. Determinations of cocaine-induced supersensitivity to norepinephrine were distorted by the norepinephrine-releasing effect of cocaine. Reliable values were obtained after pretreatment with reserpine (which abolished the norepinephrine-releasing effect).