A STUDY OF THE DEVELOPMENT OF TOLERANCE TO THE ACTIONS OF 1-METHYL4-(3-HYDROXYPHENYL)-4-PIPERIDYL ETHYL KETONE HYDROCHLORIDE IN DOGS

¹ Department of Pharmacology, University of Michigan, Ann Arbor, Michigan, and Biology Division, Sterling-Winthrop Research Institute, Rensselaer, New York

The daily administration of WIN 1539 to dogs for seven weeks produced tolerance to the analgesic, sedative, and hyperglycemic actions of the drug. No tolerance developed to the drug-induced bradycardia or hypothermia. Recovery from the tolerance occurred in one to two weeks following withdrawal. Tolerance did not develop as rapidly to WIN 1539 as to morphine. Anorexia and loss of weight was not as marked in the animals receiving WIN 1539 as in those receiving morphine.

A slight increase in heart rate, slight hyperglycemia, excitability and rest-lessness were the only symptoms noted following withdrawal of the drugs.

There were no significant changes in the hematological determinations in any of the animals during the course of the experiment.