STUDIES OF MORPHINE, CODEINE AND THEIR DERIVATIVES VII. DIHYDROMORPHINE (PARAMORPHAN), DIHYDROMORPHINONE (DILAUDID), AND DIHYDROCODEINONE (DICODIDE)

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

Dihydromorphine, like other hydrogenated derivatives, is less convulsant and more analgesic than morphine. Its emetic effect is about equal to that of morphine, it produces less general depression, and is about four times as toxic as the latter substance.

Dihydromorphinone (Dilaudid) is more active than morphine in some respects, but it is also more toxic. A comparison of the ratios of its greater effectiveness and the ratio of its greater toxicity would not lead one to expect a greater margin of safety. Its emetic effect is qualitatively like that of morphine, but quantitatively favors a lower incidence of vomiting at any dose. Its repeated administration to dogs and monkeys leads to the development of tolerance, a little less rapidly than with morphine, and to the occurrence of "abstinence" symptoms which are only slightly less severe than after similar administration of morphine.

Dihydrocodeinone (Dicodide) is more active than codeine but in most respects less active than morphine. Compared to dihydromorphinone, from which it differs only in the methylation of the phenolic hydroxyl, it shows the usual difference associated with this chemical change, increased convulsant action and decreased activity in other respects. Its repeated administration to dogs and monkeys leads to the development of tolerance but more slowly than with morphine or Dilaudid and to the occurrence of "abstinence" symptoms which are less severe than with either of the other two substances.