Zomepirac

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Zomepirac
Clinical data
Routes of
administration		By mouth
ATC code
Legal status
Legal status
  • withdrawn
Identifiers
  • 2-[5-(4-Chlorobenzoyl)-1,4-dimethyl-pyrrol-2-yl]acetic acid
JSmol)
  • 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) checkY
  • Key:ZXVNMYWKKDOREA-UHFFFAOYSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Zomepirac is an orally effective

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by doctors in many situations and obtained a large share of the analgesics market; however, it was subsequently withdrawn in March 1983 due to its tendency to cause serious anaphylaxis in a small, but unpredictable, subset of the patient population.[1][2]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 The chemical structure differs from other NSAIDs in that the central benzene ring has been replaced by a pyrrole.

Mechanism of action

Zomepirac is a

prostaglandin synthetase inhibitor.[12]

Anaphylaxis

Zomepirac does not cause anaphylaxis directly, but it is metabolized by

UDP-glucuronosyltransferase (UGT) to a reactive glucuronide which binds irreversibly to plasma albumin.[13]

Synthesis

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).

Zomepirac synthesis:[14][15][16]

See also

References

  1. PMID 1514478
    .
  2. S2CID 9912756
    .
  3. ^
    PMID 7241789
    .
  4. PMID 6221886
    .
  5. PMID 7014804
    .
  6. S2CID 19347859
    .
  7. PMID 7052110
    .
  8. S2CID 7637029
    .
  9. S2CID 45366160
    .
  10. S2CID 41806718
    .
  11. S2CID 11808742
    .
  12. ^ DC McLeod, Zomepirac (Zomax, McNeil Pharmaceutical) Archived September 28, 2007, at the Wayback Machine, Drug Intelligence & Clinical Pharmacy: Vol. 15, No. 7, pp. 522-530.
  13. PMID 3949982
    .
  14. PMID 4683116
    .
  15. ^ DE 2102746, Carson JR, "5-Aroylpyrrole [5-aroyl pyrroles]", published 1971-08-12, assigned to McNeil Laboratories Inc. 
  16. ^ US 3752826, Carson JS, issued 1973, assigned to McNeil 
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