Antagonism of the gastrointestinal ulcerogenic effect of some nonsteroidal anti-inflammatory agents by sodium salicylate

Ezer, E.; Pálosi, E; Hajós, Gy.; Szporny, L

doi:10.1111/j.2042-7158.1976.tb02824.x

Cited by 53 publications

(14 citation statements)

References 5 publications

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“…It is well known that different antiinflamma tory compounds cause gastric mucosal le sions. The inhibitory effect of sodium salicy late, salicylic acid and acetylsalicylic acid on the ulcerogenic activity of indometacin was recently reported [1][2][3]. These findings prompted us to test the effect of morphine on gastric mucosa and on gastroulcerogenic ac tivity of indometacin.…”

Section: Introductionmentioning

confidence: 99%

Morphine Potentiates the Gastroulcerogenic Effect of Indometacin in Rats

Gyires¹,

Fürst²,

Farczadi³

et al. 1985

Pharmacology

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Morphine potentiated the ulcerogenic activity of indometacin in a dose-dependent manner when administered subcutaneously (2.5–7.5 mg/kg). However, in the case of intracerebroventricular administration, morphine failed to exert any potentiating action. Atropine (0.5 mg/kg, s.c.) and cimetidine (12.5–25 mg/kg, s.c.) decreased the ulcerogenic activity of indometacin, and the combination of indometacin/morphine in about the same degree. However, the reduced ulcerogenic activity of indometacin after atropine or cimetidine treatment could still be enhanced by morphine if it was added to the combination of indometacin/atropine or indometacin/cimetidine. Since the potentiating action of morphine was completely blocked by naloxone (1 mg/kg), this action of morphine might be mediated via opiate receptors.

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Section: Introductionmentioning

confidence: 99%

Morphine Potentiates the Gastroulcerogenic Effect of Indometacin in Rats

Gyires¹,

Fürst²,

Farczadi³

et al. 1985

Pharmacology

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“…The most convincing evidence in support of this concept is the finding that coadministration of PGs prevents induction of lesions by such drugs (2). Oral administration of salicylic acid-a weak inhibitor of cyclooxygenase (8,11,14-eicosatrienoate, hydrogen-donor:oxygen oxidoreductase, EC 1.14.99.1), the initial step in PG biosynthesis and the target of most NSAIDs-has been found to diminish gastric lesions resulting from high levels of indomethacin and other NSAIDs in rats (3). A similar action of 5-(2,4-difluorophenyl)-salicylic acid (diflunisal), an inhibitor ofcyclooxygenase of intermediate potency, has been reported (4).…”

mentioning

confidence: 99%

Multiple sites on prostaglandin cyclooxygenase are determinants in the action of nonsteroidal antiinflammatory agents.

Humes¹,

Winter²,

Sadowski³

et al. 1981

Proc. Natl. Acad. Sci. U.S.A.

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Evidence is presented to show that nonsteroidal antiinflammatory drugs react with two sites on the cyclooxygenase (8,11,14-eicosatrienoate, hydrogen-donor:oxygen oxidoreductase, EC 1.14.99.1). Although the degree of interaction with the catalytic site determines the potency of such compounds, interaction with the supplementary site is also obligatory for efficacy as cyclooxygenase inhibitors and may explain the selectivity of such drugs in inhibiting the cyclooxygenase but not the lipoxygenase pathway. Drugs that interact more effectively with the supplementary site than with the catalytic site-i.e., those of weak to moderate activity as cyclooxygenase inhibitors-are shown to prevent inhibition ofthe enzyme by indomethacin. Compounds in this class are also capable of blocking the ulcerogenic action of indomethacin, which suggests that this antiulcerogenic property stems from a direct action at the level of the cyclooxygenase in the stomach.There are a number of reports indicating that the ulcerogenic action of high doses of nonsteroidal antiinflammatory drugs (NSAIDs) is secondary to a depression of prostaglandin (PG) synthesis in the stomach (1, 2). The most convincing evidence in support of this concept is the finding that coadministration of PGs prevents induction of lesions by such drugs (2). Oral administration of salicylic acid-a weak inhibitor of cyclooxygenase (8,11,14-eicosatrienoate, hydrogen-donor:oxygen oxidoreductase, EC 1.14.99.1), the initial step in PG biosynthesis and the target of most NSAIDs-has been found to diminish gastric lesions resulting from high levels of indomethacin and other NSAIDs in rats (3). A similar action of 5-(2,4-difluorophenyl)-salicylic acid (diflunisal), an inhibitor ofcyclooxygenase of intermediate potency, has been reported (4). In view of the requirement for endogenous synthesis of PGs for homeostasis ofthe stomach, these findings with both salicylate and diflunisal could be due to their ability, after oral administration, to prevent the local transport of indomethacin to the active site on stomach cyclooxygenase or due to direct competition with indomethacin for a common site on the enzyme. The recent finding that salicylic acid also blunts the ulcerogenic action of indomethacin when administered parenterally may be interpreted to support this latter possibility (5). To explore this question and its possible relation to ulcerogenicity, a number of NSAIDs were examined for their ability to counter the effect of indomethacin in inhibiting cyclooxygenase activity in vitro and to suppress indomethacin-induced gastric lesions in vivo. MATERIALS AND METHODSPG Cyclooxygenase. The NSAIDs and surfactant S10-7 (6) were obtained from N. Jensen and R. W. Egan, respectively, of these laboratories. Arachidonic acid was purchased from Sigma. Other materials were obtained from standard suppliers.Microsomes containing cyclooxygenase activity were prepared from ram seminal vesicles as described (7). The NSAIDs were incubated for 2 min at 30'C with approximately 3 mg of micro...

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“…glandin synthesis (Ziel, personal Palosi, Hajos & Szporny, 1976). Recently Lefort and (Taichman, Creighton, Stephenson & Tsai, 1972;Vargaftig (1978) and Vargaftig (1978) have demon Tsai et al, 1973;Taichman & Tsai, 1975).…”

Section: Discussionmentioning

confidence: 99%

Mechanisms of Forssman‐induced Bronchospasm and Their Inhibition

Butler

Smith

1981

British J Pharmacology

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1 The bronchospasm induced in the guinea-pig by the injection of Forssman antiserum was biphasic in nature in both the sublethal and the lethal reaction. 2 The development of both phases of the bronchospasm in the sublethal reaction was dependent upon the presence of the intact complement system and circulating platelets. In the lethal reaction the phase II bronchospasm did not appear to depend on these factors. 3 The compounds used in this study inhibited phase I bronchospasm of the sublethal reaction in the order. methysergide > indomethacin > aspirin = sulphinpyrazone and phase II in the order, indomethacin > sulphinpyrazone > aspirin. Methysergide was inactive. 4 Aspirin, indomethacin and sodium salicylate all prevented the inhibitory action of sulphinpyrazone in reducing the phase XI bronchospasm of the sublethal reaction in the order, indomethacin > sodium salicylate > aspirin. when the drugs were administered prior to sulphinpyrazone. 5 The inhibitory action of aspirin on the sulphinpyrazone effect could be prevented by administering sulphinpyrazone before aspirin. All drug-induced inhibitions of sulphinpyrazone by aspirin, indomethacin and sodium salicylate were dose-dependent.

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Antagonism of the gastrointestinal ulcerogenic effect of some nonsteroidal anti-inflammatory agents by sodium salicylate

Cited by 53 publications

References 5 publications

Morphine Potentiates the Gastroulcerogenic Effect of Indometacin in Rats

Morphine Potentiates the Gastroulcerogenic Effect of Indometacin in Rats

Multiple sites on prostaglandin cyclooxygenase are determinants in the action of nonsteroidal antiinflammatory agents.

Mechanisms of Forssman‐induced Bronchospasm and Their Inhibition

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