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.
Flanigan
M J
MJ
Department of Physiology, University of the Witwatersrand Medical School, Parktown, Johannesburg, South Africa.
Accone
Q
Q
Laburn
H P
HP
D000639:Amitriptyline / Q000494:pharmacology*; D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005334:Fever / Q000209:etiology / Q000503:physiopathology*; D008070:Lipopolysaccharides; D011817:Rabbits; D011897:Random Allocation
D008070:Lipopolysaccharides; D000639:Amitriptyline