|Chemical and physical data|
|Molar mass||291.729 g/mol|
|3D model (JSmol)|
Zomepirac is an orally effective nonsteroidal anti-inflammatory drug (NSAID) that has antipyretic actions. It was developed by McNeil Pharmaceutical, approved by the FDA in 1980, and sold as the sodium salt zomepirac sodium, under the brand name Zomax. 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by doctors in many situations and obtained a large share of the analgesics market; however, it was subsequently withdrawn in March 1983 due to its tendency to cause serious anaphylaxis in an unpredictable subset of the patient population.
Zomepirac was indicated for the management of mild to severe pain. Multiple clinical trials demonstrated zomepirac to be more effective than aspirin or codeine alone and to be as effective as analgesic combinations containing codeine or other opioids. Zomepirac provided analgesia comparable with usual intramuscular doses of morphine in postoperative pain and that with long-term use, neither tolerance to its analgesic effect nor psychological or physical dependence had been demonstrated.
Zomepirac is the sodium salt of 5-(4-chlorobenzoyl)-1,4 dimethyl-1H-pyrrole-2-acetate dihydrate. It is a pyrrole-acetic acid which is structurally related to tolmetin. The chemical structure differs from other NSAIDs in that the central benzene ring has been replaced by a pyrrole.
Mechanism of action
Zomepirac can be synthesized from diethyl 1,3-acetonedicarboxylate, chloroacetone, and aqueous methylamine (MeNH2) via modification of the Hantzsch pyrrole synthesis to give intermediate 1. Saponification, monoesterification, and thermal decarboxylation gives ester 2. This is acylated with N,N-dimethyl-p-chlorobenzamide, and finally saponification gives zomepirac (3).
- Peter H. Rheinstein, Reporting of adverse drug events: a key to postmarketing drug safety, American Family Physician, Sept, 1992
- Mark P. Grillo and Fengmei Hua, IDENTIFICATION OF ZOMEPIRAC-S-ACYL-GLUTATHIONE IN VITRO IN INCUBATIONS WITH RAT HEPATOCYTES AND IN VIVO IN RAT BILE, Drug Metabolism and Disposition, August 19, 2003
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- Smith, P. C.; McDonagh, A. F.; Benet, L. Z. (1986). "Irreversible binding of zomepirac to plasma protein in vitro and in vivo". Journal of Clinical Investigation. 77 (3): 934–939. doi:10.1172/JCI112392. PMC 423485
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- Carson, John R.; Wong, Stewart (1973). "5-Benzoyl-1-methylpyrrole-2-acetic acids as antiinflammatory agents. 2. 4-Methyl compounds". Journal of Medicinal Chemistry. 16 (2): 172. doi:10.1021/jm00260a023. PMID 4683116.
- J. R. Carson, DE 2102746 ; idem, U.S. Patent 3,752,826 (1971, 1973 both to McNeil).