THE EFFECTS OF MORPHINE AND ITS DERIVATIVES ON INTESTINAL MOVEMENTS I. MORPHINE AND THE CODEINE ISOMERS

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

1. Morphine, codeine, isocodeine, pseudocodeine, and allopseudocodeine in suitable doses cause a decrease in rhythmic frequency, an increase in rhythmic amplitude, an increase in peristalsis and an increase in tone of the ileum (dogs).

2. With the doses used a sufficient quantity of the drug to produce an effect is usually absorbed within two to ten minutes after the subcutaneous injection.

3. The effectiveness of these compounds in decreasing rhythmic frequency may roughly be expressed by M:I:C:P:A = 100:25:8:3:1.

4. A comparison of the minimal doses necessary to cause a rise in tone gives the relationship M:I:C:P:A = 100:19-58:8-15:4-5:2.

5. A phenolic hydroxyl in the 3-position, an alcoholic hydroxyl in the 6-position and a double bond in the 7-8 position are not necessary to obtain the morphine-like effects on intestinal movements. However, methylation of the phenolic hydroxyl and the position of the alcoholic hydroxyl profoundly modify the relationship between dose and effect.

6. A comparison of the results on the ileum of dogs with those on intestinal evacuation in rabbits indicates that modification of the chemical structure may have produced a selective variation in pharmacodynamic effect.