STUDIES IN ANALGESIA: PIPERIDINE DERIVATIVES WITH MORPHINE-LIKE ACTIVITY

¹ Department of Pharmacology, Hoffmann-LaRoche, Inc., Nutley, N. J.

1. A new series of piperidine derivatives has been examined for analgesic activity and other pharmacological actions.

2. Some of the compounds examined were found to produce analgesia in doses of 1/3 to 1/2 that of morphine, as measured in rats by a modified Hardy-Wolff technique.

3. The duration of analgesic action of the highly active compounds was slightly shorter than that of morphine.

4. Two of the highly active compounds were compared with morphine for the development of tolerance and were found to have considerably less effect in developing tolerance than morphine.

5. The relative safety of the highly active compounds proved to be 1/3 that of morphine and 7 times that of Demerol when the criteria were fatal doses in mice and analgesia in rats.

6. Symptoms produced by successively increasing doses were those of central stimulation.

7. A few of the compounds could cause catalepsy in rats.

8. The compounds tested possessed high degree of spasmolytic action, both neurotropic and myotropic, but since the analgesic doses are so low this is likely to be unimportant.