Effects of Anti-inflammatory Drugs on Prostaglandin Biosynthesis

Flower, Roderick J.; Gryglewski, R; Herbaczńska-Cedro, K.; Vane, John R.

doi:10.1038/newbio238104a0

Cited by 427 publications

(120 citation statements)

References 17 publications

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“…The antagonism was seen with low concentrations of the antiinflammatory drugs, within the range known to inhibit prostaglandin biosynthesis in other tissues (Vane, 1971;Ferreira, Moncada & Vane, 1971;Smith & Willis, 1971;Flower et al, 1972). The antagonism was unlikely to be due to an unrelated non-specific action of these drugs; for instance, on the oxytocin receptor, because no antagonism was seen on the duck pulmonary vein, or even on uteri from pregnant rats.…”

Section: Discussionmentioning

confidence: 97%

“…We have used indomethacin and meclofenamate, both' potent inhibitors of prostaglandin biosynthesis (Flower, Gryglewski, Herbaczynska-Cedro & Vane, 1972) to study the contribution of intramural prostaglandin production to spontaneous and drug-induced contractions of the rat isolated uterus. Contractions of the non-pregnant isolated uterus from the rat elicited by oxytocin were *Present address: Department of Pharnacology, The Medical School, University Walk, Bristol BS8 ITI).…”

Section: Introductionmentioning

confidence: 99%

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The contribution of prostaglandin production to contractions of the isolated uterus of the rat

Vane

Williams

1973

British J Pharmacology

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190

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Summary1. Indomethacin and meclofenamate, both of which are potent inhibitors of prostaglandin synthetase, antagonized the contractor effects of oxytocin on the isolated uterus from the non-pregnant rat. Contractions induced by acetylcholine or prostaglandin F2a were not antagonized.2. Uteri from rats 17-22 days pregnant exhibited intermittent spontaneous contractions when used as isolated preparations. They also released prostaglandin-like activity (mainly similar to F2a) into the bathing fluid. Both the prostaglandin release and the uterine activity were abolished by indomethacin. Activity could be restored by addition of low concentrations of prostaglandin E2 or F2a.3. The release of prostaglandin F2a-like activity by the uteri increased dramatically on the expected day of delivery (day 22). 4. The results add force to the hypothesis that the spontaneous activity of some isolated organs is due to an intramural prostaglandin generation, and that increased uterine prostaglandin production contributes to the expulsion of the foetus.

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Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

The contribution of prostaglandin production to contractions of the isolated uterus of the rat

Vane

Williams

1973

British J Pharmacology

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190

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“…A rise in blood pressure and decreased heat loss with subsequent hyperthermia due to vasocontriction could also be expected as the result of inhibition of the subcutaneous administration. However, sodium meclofenamate and indomethacin are both well absorbed (19) and inhibit effectively the synthesis of prostaglandins even at considerably lower doses than those used in the present experiments (20). It thus seems unlikely that the potentiation of the central effects of PGF 2 0' by sodium meclofenamate could be entirely due to the inhibition of prostagIandin synthesis.…”

Section: Effects Of Intracerebroventricular Pgf 2 a In Sodium Mecmentioning

confidence: 50%

Central cardiovascular and thermal effects of prostaglandin F2α in rats

1979

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Administration of PGF 2IX (0.2-6.4 J.lg) into the lateral cerebral ventricle (i.c.v.) induced dosedependent increases in blood pressure , heart rate and body temperature in urethane-anaesthetised rats, but had no effect on these parameters when the same dose range was administered intravenously. Peripheral pretreatment with sodium meclofenamate (50 mg/kg s.c.) sltifted all the dose-response curves for PGF 2IX (i.c.v.) to the left, but indomethacin (50 mg/kg s.c.) did not significantly affect those changes. Central pretreatment with sodiurn meclofenamate or indomethacin (1.25 mg per rat i.c.v.) failed to modify significantly the effects of centrally administered PGF 2IX'The results support previous suggestions that PGF 2IX may participate in the central control of the cardiovascular and thermoregulatory systems, and also suggest that there may be differences in the sites and/or modes of action between sodiurn meclofenamate and indomethacin.

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“…T h e suppressive effects of phenylbutazone and indomethacin in this model of inflammation are well known. Their mechanism of action is not completely understood but is believed to be mediated through the suppression of prostaglandin biosynthesis (17,18). T h e slope of the oral dose-response regression line for colchicine differs from that of indomethacin and phenylbutazone, suggesting a different mechanism of action.…”

Section: Discussionmentioning

confidence: 99%

Mechanism of action of colchicine

Chang

1975

Arthritis & Rheumatism

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Colchicine suppresses the development of carrageenan‐induced edema in the rat with a minimum effective oral dose of 6.0 mg/kg. The slope of the dose‐response regression line for colchicine differs significantly from that of indomethacin and phenylbutazone. Based on the dosages required to achieve a 50% suppression of this inflammation, colchicine is 0.6 and 1.5 times as potent as indomethacin and phenylbutazone, respectively. In the reversed passive Arthus reaction in the rat, the suppressive activity of colchicine is at least 50 times that of indomethacin and 100 times that of phenylbutazone. The possible significance of these results with regard to the unique effectiveness of colchicine in the treatment of gout is discussed.

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Effects of Anti-inflammatory Drugs on Prostaglandin Biosynthesis

Cited by 427 publications

References 17 publications

The contribution of prostaglandin production to contractions of the isolated uterus of the rat

The contribution of prostaglandin production to contractions of the isolated uterus of the rat

Central cardiovascular and thermal effects of prostaglandin F2α in rats

Mechanism of action of colchicine

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