Amitriptyline attenuates the febrile response to a pyrogen in rabbits

We investigated the effect of a tricyclic antidepressant (TCA) agent on fever in rabbits. In the first series of experiments, the TCA agent amitriptyline hydrochloride (AMI) was administered intraperitoneally (i.p.) at a dose of 1 mg/kg or 10 mg/kg daily for three weeks. The rabbit's response to intravenous (i.v.) injection of 0.1 micrograms/kg of the lipopolysaccharide (LPS) of Salmonella typhosa was tested on a weekly basis. In the second series of experiments, rabbits were given simultaneous i.v. injections of either 1 mg/kg or 10 mg/kg of AMI together with 0.1 microgram/kg of LPS. After two weeks of chronic i.p. administration of 10 mg/kg AMI, and for the remainder of the experimental period, the rabbit's response to the LPS was significantly attenuated when compared to control animals. When AMI was administered simultaneously with the LPS, a significant dose-dependent antipyresis was observed from 50 minutes after injection, compared to the response of control animals. AMI had no effect on the body temperature of afebrile animals.