Abstract

By means of the substitution technique, data were obtained on the potency and duration of physical dependence action of each of ten related drugs of the morphine, codeine series. From comparisons of pairs of drugs, differing from each other in only one structural respect, it would appear that in so far as physical dependence action is concerned:

(a) Methylation of the phenolic OH reduces potency and prolongs action,

(b) Replacement of the alcoholic OH by H or O increases potency and shortens the action,

(c) Spatial shift of the alcoholic OH results in irregular effects, and

(d) Saturation of the C-7, 8 double-bond tends to increase both the potency and duration of action.

These findings are qualitatively similar to those of Small and Eddy (1, Part I) in so far as the effects of (a) methylation of the phenolic OH and (b) replacement of the alcoholic OH by H or O are concerned, but are qualitatively somewhat dissimilar to their findings on the effects of (c) spatial shift of the alcoholic OH and (d) saturation of C-7, 8 double bond. The dissimilarities can be considered favorable to the assumption of a dissociation of physical dependence action from other morphine effects. None of the types of chemical modification mentioned in this report caused reductions in both duration and intensity of physical dependence action.