A Modified Class Demonstration of Difference Between Ephedrine and Epinephrine Blood-Pressure Response After Cocaine

The demonstration of cocaine sensitization for epinephrine and desensitization for ephedrine according to Sollmann and Hanzlik 1 calls for the following sequence of administration in a doubly vagotomized dog under barbital anesthesia: Epinephrine (0.05 mg. per kg.), ephedrine (2.5 mg. per kg., both intravenously), cocaine (10 mg. per kg., hypodermically), then repetition of the epinephrine and ephedrine injections after suitable intervals of time.

The epinephrine dosage should be 10 times less 1 and even as low as 0.002 mg. is very satisfactory in atropinized dogs under amytal anesthesia.

In regard to the ephedrine desensitization by cocaine we ran 3 experiments, each with a proper control without cocaine, using the same procedure as above, but only 2 mg. of ephedrine per kg. In 2 of these pairs of experiments we could not tell any difference between the cocaine and the control experiment; the second ephedrine dose was given one hour after the first in all cases. Also, in another study involving 30 dogs with even sex distribution and graded sizes, the average second ephedrine blood-pressure rise in terms of percentage of the first ephedrine rise was 53.3 with a standard deviation of 9.5 when ephedrine was followed by ephedrine, whereas the values for another 30 dogs was 40.0, standard deviation 11.4, when we gave ephedrine, cocaine and ephedrine. Thus, although the average is 25% lower when cocaine is given, the variability in response is so great that in many cases the ephedrine desensitization to itself would give values about the same as those obtained after ephedrine and cocaine, and in some cases would give even higher values than in the control experiment.

That cocaine sensitizes to epinephrine and depresses the ephedrine response may be demonstrated to a class more clearly as follows, using atropinized dogs, anesthetized with amytal.