Original communication| Volume 1, ISSUE 4, P564-580, April 1937

A comparative study of the physiologic activity of cobefrin and epinephrine

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      In this comparative study of cobefrin and epinephrine, it has been shown that these two substances have many properties in common, and that, for the most part, their physiologic behavior is identical. There are, however, several differences which are noteworthy. Both substances produce similar increases in the blood pressure of test animals, with the exception that the activity of cobefrin generally endures slightly longer than that of epinephrine. The duration of the pressor response produced by comparable doses of cobefrin is midway between that of epinephrine and ephedrine. Epinephrine causes a more marked but shorter pressor response than does ephedrine. Cobefrin gives the same abrupt pressor response as does epinephrine; the pressor response of cobefrin lasts longer than that of epinephrine, but does not endure as long as that of ephedrine.
      Barger and Dale pointed out that the maximal pressor activity of epinephrine and allied compounds was dependent on the introduction of hydroxyl groups on the para and meta positions in the basic benzene ring. Ephedrine does not have these hydroxyl groups, which probably accounts for the fact that it has less vasopressor activity.
      The presence or absence of vagal reflexes during the studies of the effects of epinephrine and cobefrin on the blood pressure were not constant in occurrence under any type of anesthesia. As a rule, neither substance gave evidence of a reflex vagal slowing with a concomitant decrease in the blood pressure. The advantage which a few clinical investigators have claimed for cobefrin is that it does not produce reflex vagal slowing of the heart. This finding was substantiated. The results which were obtained with commercial epinephrine were comparable with those obtained with cobefrin. Consequently, the use of cobefrin instead of epinephrine would appear to have no advantage in this respect. One outstanding and important difference between these closely allied compounds is that cobefrin is active when administered by mouth while epinephrine is not. Herein lies the one major difference in the action of these two substances.
      Cobefrin was found to be just as effective as epinephrine in stimulating the perfused isolated heart of the rabbit, and the ability of cobefrin to cause relaxation of a rhythmically contracting uterus of a virgin guinea pig or to relieve bronchospasm was identical with that of epinephrine. To determine the site of destruction of cobefrin in the body, the Starling heart-lung, heart-lung-liver, and heart-lunghindlimb perfusion preparations were employed. It was found that practically none of the cobefrin was inactivated in the heart-lung perfusion experiments, which fact coincides directly with the results of Elliott's experiments with epinephrine. However, the heart-lung-liver and the heart-lung-hindlimb perfusion experiments indicated definitely that any large capillary bed, with the exception of that of the lungs, serves as a site for the elimination of cobefrin. The liver is by no means as specific an organ for the inactivation of cobefrin as it is for the inactivation of nicotine or novocain. Studies on the blood sugar of dogs showed that epinephrine and cobefrin were equally potent in producing definite increases in the values for the blood sugar, provided the animals were in a proper state of nutrition.
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