ANALGESIC ACTION OF 3-HYDROXY-N-METHYL MORPHINAN HYDROBROMIDE (DROMORAN)

¹ Pharmacology Department, Hoffmann-La Roche Inc., Nutley 10, N. J.

Dromoran (Nu-2206) is a synthetic substitute for morphine which lacks only the ether-oxygen bridge of dihydrodesoxymorphine-D. The analgesic activity, by the subcutaneous route, was found to be four times as strong as morphine and about twice as long in duration. By the oral route, Dromoran was slightly stronger than methadone and longer in duration of action. Tolerance to the analgesic effects developed at about the same rate as with morphine. Respiration of unanesthetized rabbits was decreased by doses of Dromoran which were about one-fourth those of morphine and the duration of action was also longer. The compound was spasmogenic to the dog intestine as measured in a Thiry-Vella loop but was nearly inactive on isolated rabbit intestine. Dromoran was three to six times as toxic as morphine in several species but about half as toxic as methadone. Toxic doses produced characteristic morphine effects in animals. The safety factor is slightly less than that for morphine but at least twice that of methadone.

The l-form of the racemic mixture, Dromoran, has twice the analgesic activity and respiratory depressant action of the dl-mixture and equal toxicity.