THE RESPIRATORY EFFECTS OF MORPHINE, CODEINE AND RELATED SUBSTANCES II. THE EFFECT OF DIHYDROCODEINE, DIHYDROISOCODEINE, DIHYDROALLOPSEUDOCODEINE AND DIHYDROPSEUDOCODEINE

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

Dihydrocodeine, dihydroisocodeine, dihydropseudocodeine and dihydroallopseudocodeine have been compared as to their effectiveness in decreasing the rabbit's respiratory rate, minute volume and sensitivity to stimulation by carbon dioxide. The minimum doses (milligrams per kilogram of the base) required to decrease the respiratory activity are (a) dihydroisocodeine 0.6 to 1.3; (b) dihydrocodeine 2.5; (c) dihydroallopseudocodeine 3.1 to 6.2; dihydropseudocodeine 73 to 127. Hydrogenation of isocodeine and allopseudocodeine definitely increases the effectiveness of these drugs in depressing respiration. Hydrogenation of pseudocodeine has little or no effect on its action on respiration. Hydrogenation of codeine reduces its convulsant action and for this reason dihydrocodeine has the greater effect in depressing respiration at doses greater than 8 mgm. per kilogram (base). At doses below this the drugs are equally effective.