Evaluation of the Analgesic Properties of Zomepirac

Pruss, T. P.; Gardocki, Joseph F.; Taylor, Richard J. K.; Muschek, Lawrence D.

doi:10.1002/j.1552-4604.1980.tb01701.x

Cited by 49 publications

(7 citation statements)

References 9 publications

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“…The high doses required in this test also produced behavioural side effects which may have indirectly interfered with the animals ability to writhe, in addition to exerting a specific antinociceptive action. Since the doses required to inhibit zymosan-induced writhing were higher than those reported for paracetamol in most animal models of inflammatory pain (Vinegar et al, 1976;Winter et al, 1979;Pruss et al, 1980;Foote et al, 1988), it seems possible that there is some aspect of this model that makes it particularly unresponsive to paracetamol. The doses of paracetamol which inhibited writhing also reduced the synthesis of PGI2, as indicated by the reduced levels of immunoreactive 6-keto-PGF1,.…”

Section: Discussionmentioning

confidence: 91%

The antinociceptive activity of paracetamol in zymosan‐induced peritonitis in mice: the role of prostacyclin and reactive oxygen species

Doherty¹,

Beaver²,

Chan³

et al. 1990

British J Pharmacology

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1 Oral administration of high doses of paracetamol (600mg kg-1 or more) resulted in inhibition of the writhing and reduced the levels of prostacyclin (PGI2, measured as 6-keto-PGF1.) induced by intraperitoneal administration of zymosan in mice. The high oral doses of paracetamol required were accompanied by behavioural toxicity which may have contributed to the inhibition of writhing. 2 The number of writhes per mouse and the proportion of mice writhing at least once correlated significantly with the levels of 6-keto-PGF1,. However, inhibition of writhing by paracetamol occurred at higher levels of 6-keto-PGF1, than was previously observed with acidic non-steroidal anti-inflammatory agents.3 When injected i.p., PGI2, carbacyclin and iloprost (agonists at the PGI2 receptor) induced writhing. Intraperitoneal injection of PGI2 reversed the inhibition of writhing induced by indomethacin (1 mgkg-', p.o.) but not that induced by oral administration of paracetamol. 4 Paracetamol at 800mgkg-1, p.o., inhibited carbacyclin-induced writhing but indomethacin at lmgkg-1 p.o. did not. Paracetamol administered i.p. at 100mgkg-1 reduced the peritoneal levels of 6-keto-PGF1, and inhibited zymosan-induced but not carbacyclin-induced writhing and did not produce behavioural toxicity. 5The in vitro potency of paracetamol as a prostaglandin synthesis inhibitor is known to be reduced by the presence of lipid peroxides. However, no lipid peroxides, measured as thiobarbituric acid reactive material, were detected in the peritoneal lavage fluid of zymosan-injected mice. 6 Intraperitoneal administration of a mixture of superoxide dismutase and catalase reduced detectable superoxide anion by 98% without inhibiting the writhing response to zymosan or the antinociceptive potency of paracetamol. 7 The data are consistent with the suggestion that inhibition of PGI2 synthesis in the peritoneal cavity by paracetamol is responsible for only a part of its antinociceptive activity in this test. However, extremely high oral doses of paracetamol were required which produced behavioural toxicity which clearly contributed to the inhibition of writhing. The low potency of paracetamol in this model cannot be attributed to the generation of lipid peroxides via the oxidative burst.

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Section: Discussionmentioning

confidence: 91%

The antinociceptive activity of paracetamol in zymosan‐induced peritonitis in mice: the role of prostacyclin and reactive oxygen species

Doherty¹,

Beaver²,

Chan³

et al. 1990

British J Pharmacology

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“…8,9 In addition, zomepirac does not carry the risk of drug tolerance or addiction, and is lacking in withdrawal symptoms even after extended use. [9][10][11][12] Overall, this study indicates that zomepirac is an effective and well-tolerated analgesic for the symptomatic treatment of patients with muscle-contraction headache who require a prescription analgesic.…”

Section: Resultsmentioning

confidence: 97%

A Double‐blind Study of Zomepirac Sodium and Placebo in the Treatment of Muscle Contraction Headache

Diamond¹,

Medina²

1981

Headache

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SYNOPSIS In a double‐blind parallel study zomepirac sodium was compared with placebo in the treatment of muscle‐contraction headache. Eighty patients with histories of recurrent muscle‐contraction headaches were given either zomepirac 100 mg, zomepirac 50 mg, or placebo. Patients submitted evaluations for pain relief and analgesic acceptability over a range of four headache episodes. In addition, global evaluations were made by the patients and by the investigator. In the first headache episode zomepirac sodium 100 mg was significantly superior to placebo in pain relief (p = 0.030), and in analgesic acceptability (p = 0.006). Average values across all episodes indicated a significant linear dose response for zomepirac in analgesic acceptability (p<0.05). Global evaluations showed zomepirac sodium 100 mg to be significantly superior to placebo (p<0.05). The incidence of adverse effects did not vary significantly among treatment groups. Results of the study suggest that zomepirac sodium will be a useful non‐narcotic agent in the treatment of recurrent muscle‐contraction headaches requiring the use of a prescription analgesic.

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“…Our analysis of literature ED50 values for the mouse ACh-assay has shown that it is certainly valid to routinely use this test as a primary screen in a battery of antialgesic assays. Table 7 shows an equation derived by stepwise multiple regression analysis which predicts the clinical dose from laboratory Pharmacologic research in the laboratory [51] and clinic [52,53] has brought about significant advances in antialgesic specificity and has produced drugs with, in certain instances, analgesic activity as efficacious as morphine, Thus, zomepirac is as active (efficacious) as morphine in cancer pain [52,53]. Pain may be acute and due to trauma, headache, dental decay, menstruation, postoperative sequale, trigeminal neuralgia or surgery.…”

Section: Discussionmentioning

confidence: 99%

The antialgesic drugs: Human therapeutic correlates of their potency in laboratory animal models of hyperalgesia

et al. 1987

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This survey discusses the correlation between the oral potency of antialgesic drugs in several pharmacology laboratories and their human oral dose in clinical practice. We also present a brief overview of a few biological assays that have been successfully used to direct the synthesis of newer antialgesic drugs. The laboratory assay that our analysis showed to be most predictive of the clinical analgesic dose is based upon the response of rats to flexion of an arthritic joint. Laboratory ED50 values from the ACh-induced abdominal constriction assay in mice are nearly as predictive while the predictive power of the yeast-induced hyperalgesia assay in rats is somewhat less. Probably because of the small number of experiments, the correlation between the efficacy of these agents in a canine model of synovitis and their clinical doses only reached borderline statistical significance (p = 0.0651). Regression equations are presented that permit calculations of single clinical analgesic doses from efficacy data in individual tests. Calculation of stepwise multiple regression showed that the clinical dose could be best predicted when efficacy data obtained in the joint flexion assay in rats and the ACh-induced constriction assay in mice are both taken into account. We have concluded that the effective doses are highly predictive of clinical efficacy because these animal assays have been designed to reflect the action of drugs upon prostanoid-induced hyperalgesia.

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Evaluation of the Analgesic Properties of Zomepirac

Cited by 49 publications

References 9 publications

The antinociceptive activity of paracetamol in zymosan‐induced peritonitis in mice: the role of prostacyclin and reactive oxygen species

The antinociceptive activity of paracetamol in zymosan‐induced peritonitis in mice: the role of prostacyclin and reactive oxygen species

A Double‐blind Study of Zomepirac Sodium and Placebo in the Treatment of Muscle Contraction Headache

The antialgesic drugs: Human therapeutic correlates of their potency in laboratory animal models of hyperalgesia

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