The Antipyretic Effect of Tilorone Hydrochloride in the Cat

Abstract

The antipyretic activity of tilorone hydrochloride was studied in conscious, unrestrained cats provided with implanted jugular venous catheters, third cerebral ventricular (i.c.v.) cannulae and retroperitoneal thermocouples. In afebrile animals, 10 mg/kg i.v. or 1 mg i.c.v. tilorone hydrochloride did not alter body temperature, but 20 mg/kg i.v. or 2 to 5 mg i.c.v. caused hypothermia and various behavioural responses. Non‐hypothermogenic doses of tilorone (i.v. or i.c.v.) antagonized hyperthermic responses to leucocytic pyrogen (i.v. or i.c.v.), bacterial pyrogen (i.c.v.) and sodium arachidonate (i.c.v.) but did not antagonize prostaglandin E1 (i.c.v.). These results indicate that tilorone has an antipyretic action within the central nervous system that is distinct from its hypothermogenic action. Although there is no published evidence to indicate that tilorone can inhibit prostaglandin synthesis peripherally, its ability to reduce hyperthermic responses to arachidonate suggests that it can inhibit prostaglandin synthesis within the brain.

The antipyretic effect of UP 517-03 in the rabbit

“…Since the hypothesis formulated by VANE in 1971 [5] postulating that antipyretics act by inhibition of the PG synthetase system, acetylsalicylic acid, paracetamol, indomethacin [9,[11][12][13][14] and more recently tilorone and flurbiprofen [15][16] have been shown in numerous studies to have an antagonistic activity on long-term hyperthermia induced by the injection of bacterial endotoxin or arachidonic acid (the precursor of PGE2) into the cerebro-spinal fluid.…”

“…In different animal species [11][12][13][14][15][16][17] this hyperthermia is linked to an increase in the concentration of brain prostaglandins [12,18]. Intraventricular injection of endotoxin can either activate mechanisms responsible for the synthesis of PG [6,7,19], inhibit in the hypothalamus the enzyme that metabolizes PGE 2 [20], considered to be a trigger in the onset of fever [12,18,21], or act on an earlier step preceding the synthesis of prostaglandins [17,22].…”

An Effective Synthesis Method for Tilorone Dihydrochloride with Obvious IFN-α Inducing Activity

“…Tilorone dihydrochloride ( 1 , Figure 1) was first reported to have antivirus activity in mice in 1970 [1,2]. Moreover, it has been gradually proved to possess extensive pharmacological functions, such as enhanced phagocytic activity of natural killer cells [3], anti-pyretic [4], anti-fibrotic [5], anti-inflammatory [6,7,8,9,10], anti-virus [11,12], anti-tumor [13,14,15], as well as interferon induction [16,17,18]. All the effects are attributed to its planar structure of a modification of the fluorenone skeleton and amino side chain [15,19,20,21].…”