THE RESPIRATORY EFFECTS OF MORPHINE, CODEINE, AND RELATED SUBSTANCES IX. THE EFFECT OF MUZZLING THE PHENOLIC HYDROXYL

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

The depressant effects upon rabbits' respiration are given for 7 derivatives of morphine in which the phenolic hydroxyl group, at carbon-3, has been muzzled by ethyl, methoxymethyl, benzyl, or dinitrophenyl. Using the "threshold" dose for depressing minute volume as a criterion of potency, we have compared these and 8 related drugs whose effects have been previously described, to ascertain whether the loss of potency associated with substitution at that point depends upon the intactness of the phenolic hydroxyl radical per se, or upon the special properties of the substituent. Dinitrophenylmorphine was stronger than morphine in small doses though weaker in doses larger than about 0.3 mgm. The remaining codeine-like compounds were all weaker than their morphine-like analogs. Among them, it seemed to make little difference whether the substituent was methyl, ethyl, methoxymethyl, or benzyl, except in one instance, when methyl (in dihydrodesoxycodeine-D, #16) proved much more depressant than benzyl (in benzyldihydrodesoxymorphine-D, #312).