Antagonism by antipyretics of the hyperthermic effect of a prostaglandin precursor, sodium arachidonate, in the cat.

Clark, William G.; Cumby, H R

doi:10.1113/jphysiol.1976.sp011386

Cited by 30 publications

(12 citation statements)

References 17 publications

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“…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].…”

Section: Discussionmentioning

confidence: 99%

The antipyretic effect of UP 517-03 in the rabbit

Hertz¹,

Chevrier²,

Dumeur³

et al. 1979

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The antipyretic effect of UP 517-03 was studied in rabbits, provided with a cannula in the lateral cerebral ventricle. Given orally as a curative treatment, UP 517-03 can abolish hyperthermic reactions induced by intracerebroventricular injection of sodium arachidonate or bacterial endotoxin. A comparison with acetylsalicylic acid and indomethacin is given. UP 517-03 does not modify the temperature of normothermic rabbits. These results suggests that the antipyretic action of UP 517-03 can be explained by an effect of this substance on the metabolism of arachidonic acid in brain.

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Section: Discussionmentioning

confidence: 99%

The antipyretic effect of UP 517-03 in the rabbit

Hertz¹,

Chevrier²,

Dumeur³

et al. 1979

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“…1. Since mepacrine, at least, is known also to inhibit cycloxygenase at high doses (Flower & Blackwell, 1976), we have examined in addition the action of those drugs on the pyrexia which follows intraventricular injection of arachidonic acid (Clark & Cumby, 1976;Laburn, Mitchell & Rosendorff, 1977;Splawinski, Gorka, Zacny & Wojtaszek, 1978).…”

Section: Introductionmentioning

confidence: 99%

Intraventricular injections of drugs which inhibit phospholipase A2 suppress fever in rabbits.

Cranston¹,

Hellon²,

Mitchell³

et al. 1983

The Journal of Physiology

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SUMMARY1. Injection of two chemically dissimilar inhibitors of phospholipase A2 (mepacrine and parabromophenacylbromide) into the cerebral ventricles of rabbits inhibited the febrile response to endogenous pyrogen given by the same route.2. The same doses of the inhibitors given intravenously did not affect the febrile response to endogenous pyrogen given into the ventricles, indicating that their action was central.3. When given intraventricularly the inhibitors did not affect the maintenance of core temperature in a cold environment, indicating that they did not impair thermoregulatory ability. 4. The inhibitors had no effect on the temperature rise following intraventricular injection of arachidonic acid.5. These observations are compatible with the proposition that one or more metabolic products of arachidonic acid other than prostaglandin are involved in pyrogenesis.

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“…Doses of tilorone refer to the hydrochloride. Saline solutions of sodium arachidonate (Nu-Chek-Prep, Inc., Elysian, Minnesota) were kept frozen at -9°C and were thawed as necessary to obtain portions for injections (Clark & Cumby, 1976). Leucocytic pyrogen and prostaglandin E1 (Upjohn) were prepared and stored respectively as described previously (Clark & Cumby, 1975 (Figure 4).…”

Section: Methodsmentioning

confidence: 99%

“…injection of endotoxin than after arachidonate (Clark & Cumby, 1976), endotoxin was given at 10 h 00 min and arachidonate at 12 h 00 min. Tilorone or saline was injected i.v.…”

Section: Lack Of Antagonism Of Prostaglandin By Tiloronementioning

confidence: 99%

“…Paracetamol and indomethacin have been shown to be more potent in reducing febrile responses to pyrogens than in antagonizing the hyperthermic response to arachidonate (Clark & Cumby, 1976), the precursor of prostaglandin E2. This suggests that, if prostaglandins mediate pyrogen-induced fevers, these antipyretics exert a major action at some step before prostaglandin synthesis.…”

Section: Introductionmentioning

confidence: 99%

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The Antipyretic Effect of Tilorone Hydrochloride in the Cat

Clark

Robins

1978

British J Pharmacology

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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.

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Antagonism by antipyretics of the hyperthermic effect of a prostaglandin precursor, sodium arachidonate, in the cat.

Cited by 30 publications

References 17 publications

The antipyretic effect of UP 517-03 in the rabbit

The antipyretic effect of UP 517-03 in the rabbit

Intraventricular injections of drugs which inhibit phospholipase A2 suppress fever in rabbits.

The Antipyretic Effect of Tilorone Hydrochloride in the Cat

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