FURTHER OBSERVATIONS ON THE PHARMACOLOGY OF `DOLOPHINE' (METHADON, LILLY)

¹ From The Lilly Research Laboratories, Eli Lilly and Company, Indianapolis 6, Indiana

1. In dogs receiving injections daily for as long as 50 days, tolerance developed to the analgesic and narcotic actions of `Dolophine', when the dose was gradually increased and the intervals of administration were shortened. No tolerance to cardiac slowing and intestinal motility effects occurred.

2. The only withdrawal phenomena noted in these dogs were tachycardia and low-grade fever.

3. Rats developed partial tolerance to the analgesic action of `Dolophine' when given a constant single daily dose for 27 days.

4. `Dolophine' resembled morphine in its action on the intestine. It increased the motility of the small bowel of unanesthetized dogs and produced constipation in rabbits and dogs.

5. Demerol stimulated the movements of the small intestine and slowed the heart rate. These results are directly opposed to those of investigators who claim an atropine-like effect for the drug.

6. Respiratory depression following `Dolophine' was adequately counteracted by d-desoxyephedrine, d-benzedrine, or ephedrine, the first-named drug being the most potent. Nikethamide and 1-n-propyl theobromine were less efficient.

7. By cross-circulation experiments the parasympathomimetic effects of `Dolophine' on heart rate and intestinal motility were shown to be of central origin.