The Significance of the Adrenal Medullary Epinephrin in the Analgesic Effects of Morphine and a Few Other Drugs in Mice

The analgesic effects of morphine and some related compounds, such as meperidine, observed by the conventional method, are supplemented by the release of epinephrine from the adrenal medulla. It is assumed that this action of epinephrine is not due to an additive synergy in the analgesic effect but to the face that the action of epinephrine on a definite higher center or centers effects synergistically in the reflex depressant action of these analgesic agants. This assumption is based on the following evidences. Prolongation of reaction time in mice by morphine and meperidine (but not by ohton), determined by the hot-plate method, was significantly reduced by adrenalectomy and this reduction was normalized by the concurrent use of epinephrine, in a small dose which in itself cannot prolong the reaction time. No such action was found in cortisone and DOCA. The effects of morphine and meperidine in prolonging the reaction time were reduced by priscol and dibenamine, as well as by tetraethylammonium salt. A large dose of pyrazolone derivatives causes, not the prolongation of reaction time but a jumping reflex response in the early stages, indicating central excitation, in part of the mice. The ratio of mice exhibiting such an early reflex increases with adrenalectomy or the administration of dibenamine, and is markedly decreased by epinephrine, insufficient to show any analgesic response by itself, and by cortisone. This action of cortisone indicates some difference in the natures of central excitation by pyrazolones and by morphine. Judging from the work of SCHAYER18, the distribution in the brain of epinephrine injected in the dose to normalize the reduced effect of morphine in the adrenalectomized mice, may also be anticipated by the epinephrine which might be released from the adrenal medulla by morphine in an amount much smaller than the "near·lethal doses9 ".