Zomepirac

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Zomepirac
Zomepirac.png
Systematic (IUPAC) name
2-[5-(4-chlorobenzoyl)-1,4-dimethyl-pyrrol-2-yl]acetic acid
Clinical data
Legal status
  • withdrawn
Routes of
administration		 oral
Identifiers
CAS Number 33369-31-2 N
ATC code M01AB04 (WHO)
PubChem CID: 5733
DrugBank DB04828 YesY
ChemSpider 5531 YesY
UNII 822G987U9J YesY
ChEBI CHEBI:35859 YesY
ChEMBL CHEMBL19490 YesY
Chemical data
Formula C15H14ClNO3
Molecular mass 291.729 g/mol
  • O=C(c1c(cc(n1C)CC(=O)O)C)c2ccc(Cl)cc2
  • InChI=1S/C15H14ClNO3/c1-9-7-12(8-13(18)19)17(2)14(9)15(20)10-3-5-11(16)6-4-10/h3-7H,8H2,1-2H3,(H,18,19) YesY
  • Key:ZXVNMYWKKDOREA-UHFFFAOYSA-N YesY
 NYesY (what is this?)  (verify)

Zomepirac is an orally effective NSAID that has antipyretic actions. It was developed by McNeil Pharmaceutical and 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by doctors in many situations and obtained a large share of the analgesics market; however, it was subsequently withdrawn in March 1983 due to its tendency to cause serious anaphylaxis in an unpredictable subset of the patient population.[1][2]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.

Mechanism of action

It is a prostaglandin synthetase inhibitor.[12]

Toxicity

Zomepirac does not cause anaphylaxis directly, but it is metabolised by UGT to a reactive glucuronide, which binds irreversibly to plasma albumin.[13]

Synthesis

A NSAID in which the benzene ring carrying the acetic acid moiety has been replaced by a pyrrole grouping is zomepirac.

Zomepirac synthesis:[14][15]

It is synthesized from Diethyl 1,3-acetonedicarboxylate, chloroacetone, and aqueous 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).

References

  1. ↑ Peter H. Rheinstein, Reporting of adverse drug events: a key to postmarketing drug safety, American Family Physician, Sept, 1992
  2. ↑ 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
  3. ↑ 3.0 3.1 Lua error in package.lua at line 80: module 'strict' not found.
  4. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  5. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  6. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  7. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  8. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  9. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  10. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  11. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  12. ↑ DC McLeod, Zomepirac (Zomax, McNeil Pharmaceutical), Drug Intelligence & Clinical Pharmacy: Vol. 15, No. 7, pp. 522-530.
  13. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  14. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  15. ↑ J. R. Carson, DE 2102746; idem, US 3752826 (1971, 1973 both to McNeil).
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