STUDIES OF MORPHINE, CODEINE AND THEIR DERIVATIVES II. ISOMERS OF CODEINE

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

Codeine and its isomers, allopseudocodeine, isocodeine and pseudocodeine, have been compared as to toxicity, and as to convulsant, depressant, analgesic, respiratory, and gastro-intestinal effects. In each case comparisons have been made with morphine also.

The order of toxicity and convulsant action was codeine (most toxic and most convulsant), allopseudocodeine, isocodeine, and pseudocodeine. The last was less than one-seventh as toxic as codeine in mice and rabbits and did not produce convulsions.

The order of analgesic effect was pseudocodeine, isocodeine, codeine and allospeudocodeine (least analgesic). The order appeared to be the same for general depressant effect.

The order of respiratory effect (depression of respiration and its response to various stimuli) was isocodeine, pseudocodeine, codeine and allopseudocodeine. The last in the dosages used appeared to be devoid of significant respiratory effect. Isocodeine was more than four times as effective in depressing respiratory reflexes as codeine, and pseudocodeine was three times as effective as codeine.

The order of gastro-intestinal effect (suppression of intestinal evacuation in each of ten rabbits) was isocodeine, pseudocodeine, allopseudocodeine and codeine (least effective).

On all counts both isocodeine and pseudocodeine appear to possess advantage over codeine.