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by doctors in many situations and obtained a large share of the analgesics market; however, it was subsequently withdrawn in March 1983 due to its tendency to cause serious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 a small, but unpredictable, subset of the patient population.[1][2]
Indications
Zomepirac was indicated for the management of mild to severe pain.[3] 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.[4][5][6][7][8][9][10] 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.[3][11]
Chemical structure
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 The chemical structure differs from other NSAIDs in that the central benzene ring has been replaced by a pyrrole.
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).
^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.
^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.