Zomepirac is an orally effectivenonsteroidal anti-inflammatory drug (NSAID) that hasantipyretic actions. It was developed byMcNeil Pharmaceutical, approved by theFDA in 1980, and sold as the sodium salt zomepirac sodium, under the brand nameZomax. Due to its clinical effectiveness, it was preferred by doctors in many situations and obtained a large share of the analgesics market; however, it was subsequently withdrawn in March 1983 due to its tendency to cause seriousanaphylaxis in a small, but unpredictable, subset of the patient population.[1][2]
Zomepirac was indicated for the management of mild to severe pain.[3] Multiple clinical trials demonstrated zomepirac to be more effective thanaspirin orcodeine alone and to be as effective as analgesic combinations containing codeine or otheropioids.[4][5][6][7][8][9][10] Zomepirac provided analgesia comparable with usualintramuscular doses ofmorphine in postoperative pain and that with long-term use, neithertolerance to its analgesic effect nor psychological orphysical dependence had been demonstrated.[3][11]
Zomepirac is the sodium salt of 5-(4-chlorobenzoyl)-1,4 dimethyl-1H-pyrrole-2-acetate dihydrate. It is apyrrole-acetic acid which is structurally related totolmetin. The chemical structure differs from other NSAIDs in that the central benzene ring has been replaced by a pyrrole.
Zomepirac can be synthesized from diethyl 1,3-acetonedicarboxylate,chloroacetone, and aqueousmethylamine (MeNH2) via modification of theHantzsch pyrrole synthesis to give intermediate1. Saponification, monoesterification, and thermal decarboxylation gives ester2. This is acylated withN,N-dimethyl-p-chlorobenzamide, and finallysaponification gives zomepirac (3).
^Grillo MP, Hua F (November 2003). "Identification of zomepirac-S-acyl-glutathione in vitro in incubations with rat hepatocytes and in vivo in rat bile".Drug Metabolism and Disposition.31 (11):1429–1436.doi:10.1124/dmd.31.11.1429.PMID14570776.S2CID9912756.
^Steele CE, Jefferson WL (1983). "A multi-centre study of zomepirac in painful conditions: an analysis of clinical data for 15,484 patients".Current Medical Research and Opinion.8 (6):382–391.doi:10.1185/03007998309111743.PMID6221886.
^Mehlisch DR, Joy ED (June 1981). "Zomepirac sodium vs APC with codeine for oral surgery pain".Journal of Oral Surgery.39 (6):426–429.PMID7014804.
^Baird WM, Turek D (April 1980). "Comparison of zomepirac, APC with codeine, codeine and placebo in the treatment of moderate and severe postoperative pain".Journal of Clinical Pharmacology.20 (4):243–249.doi:10.1002/j.1552-4604.1980.tb01704.x.PMID6991540.S2CID7637029.
^Mehlisch DR, Joy ED, Moore TE, Porter K, Stumpf AJ, Wolfe SH (April 1980). "Clinical comparison of zomepirac with APC/codeine combination in the treatment of pain following oral surgery".Journal of Clinical Pharmacology.20 (4):271–278.doi:10.1002/j.1552-4604.1980.tb01708.x.PMID6991544.S2CID45366160.
^Wallenstein SL, Rogers A, Kaiko RF, Heidrich G, Houde RW (April 1980). "Relative analgesic potency of oral zomepirac and intramuscular morphine in cancer patients with postoperative pain".Journal of Clinical Pharmacology.20 (4):250–258.doi:10.1002/j.1552-4604.1980.tb01705.x.PMID6991541.S2CID11808742.
^Carson JR, Wong S (February 1973). "5-Benzoyl-1-methylpyrrole-2-acetic acids as antiinflammatory agents. 2. The 4-methyl compounds".Journal of Medicinal Chemistry.16 (2):172–174.doi:10.1021/jm00260a023.PMID4683116.
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