Zomepirac

Indications

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.

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 The chemical structure differs from other NSAIDs in that the central benzene ring has been replaced by a pyrrole.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.

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.

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).

References

References

1. (September 1992). "Reporting of adverse drug events: a key to postmarketing drug safety". American Family Physician.
2. (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.
3. (1981). "Zomepirac sodium. A new nonaddicting analgesic". JAMA.
4. (1983). "A multi-centre study of zomepirac in painful conditions: an analysis of clinical data for 15,484 patients". Current Medical Research and Opinion.
5. (June 1981). "Zomepirac sodium vs APC with codeine for oral surgery pain". Journal of Oral Surgery.
6. (1981). "Analgesic efficacy of zomepirac sodium in patients with pain due to cancer". Journal of Clinical Pharmacology.
7. (September 1982). "Zomepirac, placebo and paracetamol/dextropropoxyphene combination compared in orthopaedic postoperative pain". British Journal of Anaesthesia.
8. (April 1980). "Comparison of zomepirac, APC with codeine, codeine and placebo in the treatment of moderate and severe postoperative pain". Journal of Clinical Pharmacology.
9. (April 1980). "Clinical comparison of zomepirac with APC/codeine combination in the treatment of pain following oral surgery". Journal of Clinical Pharmacology.
10. (March 1981). "A double-blind study of zomepirac sodium and placebo in the treatment of muscle contraction headache". Headache.
11. (April 1980). "Relative analgesic potency of oral zomepirac and intramuscular morphine in cancer patients with postoperative pain". Journal of Clinical Pharmacology.
12. DC McLeod, [http://www.theannals.com/cgi/content/abstract/15/7/522 Zomepirac (Zomax, McNeil Pharmaceutical)] {{webarchive. link. (September 28, 2007 , ''Drug Intelligence & Clinical Pharmacy'': Vol. 15, No. 7, pp. 522-530.)
13. (March 1986). "Irreversible binding of zomepirac to plasma protein in vitro and in vivo". The Journal of Clinical Investigation.
14. (February 1973). "5-Benzoyl-1-methylpyrrole-2-acetic acids as antiinflammatory agents. 2. The 4-methyl compounds". Journal of Medicinal Chemistry.
15. "5-Aroylpyrrole [5-aroyl pyrroles]".
16. {{cite patent. McNeil]]