STUDIES OF MORPHINE, CODEINE AND THEIR DERIVATIVES III. MORPHINE METHOCHLORIDE AND CODEINE METHOCHLORIDE

¹ From the Laboratory of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan

Transformation of the tertiary bases, morphine and codeine, to their quaternary ammonium salts by the formation of the methochlorides resulted in both instances in a marked diminution in pharmacological action.

Both of the methochlorides exhibited definite curare-like action demonstrable in frogs when the substance was injected into a lymph sac in the proportion of one-sixth or more of the fatal dose.

Muzzling the phenolic hydroxyl by methylation in the formation of codeine from morphine, and codeine methochloride from morphine methochloride produced the same modification of the pharmacological picture. In both cases the methylated compound showed a greater increase in spinal excitability, a greater tendency to the development of convulsions, but it was less active in the production of all of the other typical morphine effects which were studied.