THE RESPIRATORY EFFECTS OF MORPHINE, CODEINE, AND RELATED SUBSTANCES X. THE EFFECT OF SUBSTITUTING AN ADDITIONAL GROUP IN RING-THREE

¹ From the Laboratory of Pharmacology, University of Michigan Medical School, and the National Institute of Health, Washington

Ten drugs differing from morphine and related compounds by the attachment of an additional radical to ring-III in the molecule have been given in various dosages to rabbits to see how this chemical change affected the power to depress respiration. They are methyldihydromorphine, methyldihydromorphinone, methyldihydrocodeine, methyldihydrocodeinone, methyldihydrocodeinone enol acetate, ethyl-, isopropyl-, amyl-, benzyl-, and phenyl-dihydromorphinone. An eleventh substance, dihydrocodeinone enol acetate, was also studied to complete our background of analogous unsubstituted compounds. Judged by the "threshold" dose to depress respiratory minute volume, the new type of chemical alteration was found to be correlated with increased potency in two instances, with diminished potency in seven, and with no change in one. Amyldihydromorphinone was more potent than any other of the sixty-five derivatives of morphine whose respiratory effects have been studied in this laboratory. The varying result of substitution can not be accounted for entirely by the individuality of the extra radical, since one case of augmented strength, three cases of reduced strength, and the case of no change, all followed substitution of the methyl group. No satisfactory explanation is known.