Cocaine Potentiation of Epinephrine and Ephedrine Action on Uterus and Intestine.

Abstract

The work of Froehlich and Loewi 1 demonstrating that cocaine increases the sensitivity to epinephrine of the iris, urinary bladder, salivary glands and blood vessels of the cat, followed by De Eds' 2 results showing antagonism by cocaine of the pressor action of ephedrine, suggested the need for work with these drugs on other organs.

With excised strips of non-gravid uterus of the rabbit, suspended in Tyrode solution, there was a definite (20-400%) potentiation of epinephrine and ephedrine actions by cocaine. The cocaine-ephedrine potentiation was evident also on the ergotaminized rabbit uterus, no longer responsive to epinephrine, and on guinea pig uterus. Ephedrine caused contraction of both organs. These facts are important in the analysis of the site of action of ephedrine, and possibly also of the sensitizing action of cocaine.

It is to be noted that the above potentiations were upon organs contracted by epinephrine or ephedrine. Reports by Lindblom 3 and Halsey 4 indicated a similar cocaine sensitization of the small bowel to the inhibitory action of epinephrine. We, however, have made 15 trials in 8 animals, without being able to demonstrate any definite sensitization of the small bowel of the rabbit or the small or large bowel of the guinea pig toward either epinephrine or ephedrine. The more frequent finding was an antagonism of the inhibitory action of epinephrine or ephedrine by cocaine.

No change in pH resulted from adding the cocaine solution to the organ bath, hence pH changes could not account for the sensitization.