Zomepirac

Last updated
Zomepirac
Zomepirac.svg
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  • withdrawn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
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.046.780 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C15H14ClNO3
Molar mass 291.73 g·mol−1
3D model (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) Yes check.svgY
  • Key:ZXVNMYWKKDOREA-UHFFFAOYSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

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by doctors in many situations and obtained a large share of the analgesics market; however, it was subsequently withdrawn in March 1983 due to its tendency to cause serious anaphylaxis in a small, but unpredictable, subset of the patient population.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]

Contents

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 The chemical structure differs from other NSAIDs in that the central benzene ring has been replaced by a pyrrole.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

See also

Related Research Articles

<span class="mw-page-title-main">Analgesic</span> Drugs used to achieve relief from pain

An analgesic drug, also called simply an analgesic, antalgic, pain reliever, or painkiller, is any member of the group of drugs used for pain management. Analgesics are conceptually distinct from anesthetics, which temporarily reduce, and in some instances eliminate, sensation, although analgesia and anesthesia are neurophysiologically overlapping and thus various drugs have both analgesic and anesthetic effects.

<span class="mw-page-title-main">Ketoprofen</span> NSAID analgesic medication

Ketoprofen is one of the propionic acid class of nonsteroidal anti-inflammatory drugs (NSAID) with analgesic and antipyretic effects. It acts by inhibiting the body's production of prostaglandin.

<span class="mw-page-title-main">Paracetamol</span> Common medication for pain and fever

Paracetamol, or acetaminophen, is a non-opioid analgesic and antipyretic agent used to treat fever and mild to moderate pain. It is a widely available over-the-counter drug sold under various brand names, including Tylenol and Panadol.

<span class="mw-page-title-main">Opioid</span> Psychoactive chemical

Opioids are a class of drugs that derive from, or mimic, natural substances found in the opium poppy plant. Opioids work on opioid receptors in the brain and other organs to produce a variety of morphine-like effects, including pain relief.

<span class="mw-page-title-main">Etoricoxib</span> COX-2 selective NSAID medication

Etoricoxib, sold under the brand name Arcoxia, is a selective COX-2 inhibitor developed and commercialized by Merck. It is approved in 63 countries worldwide as of 2007, except the United States where the Food and Drug Administration sent a Non Approvable Letter to Merck and required them to provide additional data.

<span class="mw-page-title-main">Orphenadrine</span> Muscle relaxant drug

Orphenadrine is an anticholinergic drug of the ethanolamine antihistamine class; it is closely related to diphenhydramine. It is a muscle relaxant that is used to treat muscle pain and to help with motor control in Parkinson's disease, but has largely been superseded by newer drugs. It is considered a dirty drug due to its multiple mechanisms of action in different pathways. It was discovered and developed in the 1940s.

<span class="mw-page-title-main">Nalbuphine</span> Opioid analgesic

Nalbuphine, sold under the brand names Nubain among others, is an opioid analgesic which is used in the treatment of pain. It is given by injection into a vein, muscle, or fat.

<span class="mw-page-title-main">Levonantradol</span> Chemical compound

Levonantradol (CP 50,556-1) is a synthetic cannabinoid analog of dronabinol (Marinol) developed by Pfizer in the 1980s. It is around 30 times more potent than THC, and exhibits antiemetic and analgesic effects via activation of CB1 and CB2 cannabinoid receptors. Levonantradol is not currently used in medicine as dronabinol or nabilone are felt to be more useful for most conditions, however it is widely used in research into the potential therapeutic applications of cannabinoids.

<span class="mw-page-title-main">Lefetamine</span> Chemical compound

Lefetamine (Santenol) is a drug which is a stimulant and also an analgesic with effects comparable to codeine.

<span class="mw-page-title-main">Tolmetin</span> NSAID analgesic medication

Tolmetin is a nonsteroidal anti-inflammatory drug (NSAID) of the heterocyclic acetic acid derivative class.

<span class="mw-page-title-main">Dezocine</span> Opioid analgesic

Dezocine, sold under the brand name Dalgan, is an atypical opioid analgesic which is used in the treatment of pain. It is used by intravenous infusion and intramuscular injection.

<span class="mw-page-title-main">Ciramadol</span> Opioid analgesic drug

Ciramadol (WY-15,705) is an opioid analgesic that was developed in the late 1970s and is related to phencyclidine, tramadol, tapentadol and venlafaxine. It is a mixed agonist-antagonist for the μ-opioid receptor with relatively low abuse potential and a ceiling on respiratory depression which makes it a relatively safe drug. It has a slightly higher potency and effectiveness as an analgesic than codeine, but is weaker than morphine. Other side effects include sedation and nausea but these are generally less severe than with other similar drugs.

<span class="mw-page-title-main">Propiram</span> Opioid analgesic drug

Propiram is a partial μ-opioid receptor agonist and weak μ antagonist analgesic from the ampromide family of drugs related to other drugs such as phenampromide and diampromide. It was invented in 1963 in the United Kingdom by Bayer but was not widely marketed, although it saw some limited clinical use, especially in dentistry. Propiram reached Phase III clinical trials in the United States and Canada.

<span class="mw-page-title-main">Bicifadine</span> Chemical compound

Bicifadine (DOV-220,075) is a serotonin-norepinephrine-dopamine reuptake inhibitor (SNDRI) discovered at American Cyanamid as an analgesic drug candidate, and licensed to DOV Pharmaceutical in 1998 after American Cyanamid was acquired by Wyeth.

<span class="mw-page-title-main">Nefopam</span> Analgesic medication

Nefopam, sold under the brand name Acupan among others, is a centrally acting, non-opioid painkilling medication, with central stimulant and sympathomimetic properties that is primarily used to treat moderate to severe pain.

<span class="mw-page-title-main">Flupirtine</span> Non-opioid analgesic

Flupirtine is an aminopyridine that functions as a centrally acting non-opioid analgesic that was originally used as an analgesic for acute and chronic pain but in 2013 due to issues with liver toxicity, the European Medicines Agency restricted its use to acute pain, for no more than two weeks, and only for people who cannot use other painkillers. In March 2018, marketing authorisations for flupirtine were withdrawn following a European Medicines Agency recommendation based on the finding that the restrictions introduced in 2013 had not been sufficiently followed in clinical practice, and cases of serious liver injury still occurred including liver failure.

An equianalgesic chart is a conversion chart that lists equivalent doses of analgesics. Equianalgesic charts are used for calculation of an equivalent dose between different analgesics. Tables of this general type are also available for NSAIDs, benzodiazepines, depressants, stimulants, anticholinergics and others.

<span class="mw-page-title-main">Doxpicomine</span> Chemical compound

Doxpicomine is a mild opioid analgesic drug. The drug acts as a mu-opioid receptor agonist. It is of fairly low potency, with a 400 mg dose of doxpicomine approximately equivalent in pain-killing effect to 8 mg morphine or 100 mg pethidine. It has been used as a lead compound to derive further analogues, although all compounds in this family are comparatively weak mu agonists.

<span class="mw-page-title-main">EMA401</span> Chemical compound

EMA401 is a drug under development for the treatment of peripheral neuropathic pain. Trials were discontinued in 2015, with new trials scheduled to begin March, 2018. It was initially established as a potential drug option for patients suffering pain caused by postherpetic neuralgia. It may also be useful for treating various types of chronic neuropathic pain EMA401 has shown efficacy in preclinical models of shingles, diabetes, osteoarthritis, HIV and chemotherapy. EMA401 is a competitive antagonist of angiotensin II type 2 receptor (AT2R) being developed by the Australian biotechnology company Spinifex Pharmaceuticals. EMA401 target angiotensin II type 2 receptors, which may have importance for painful sensitisation.

<span class="mw-page-title-main">Pain management in children</span> Medical condition

Pain management in children is the assessment and treatment of pain in infants and children.

References

  1. ↑ Rheinstein PH (September 1992). "Reporting of adverse drug events: a key to postmarketing drug safety". American Family Physician. 46 (3): 873–874. PMID   1514478.
  2. ↑ 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. PMID   14570776. S2CID   9912756.
  3. 1 2 Lewis JR (1981). "Zomepirac sodium. A new nonaddicting analgesic". JAMA. 246 (4): 377–379. doi:10.1001/jama.246.4.377. PMID   7241789.
  4. ↑ 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. PMID   6221886.
  5. ↑ Mehlisch DR, Joy ED (June 1981). "Zomepirac sodium vs APC with codeine for oral surgery pain". Journal of Oral Surgery. 39 (6): 426–429. PMID   7014804.
  6. ↑ Stambaugh JE, Sarajian C (1981). "Analgesic efficacy of zomepirac sodium in patients with pain due to cancer". Journal of Clinical Pharmacology. 21 (11): 501–507. doi:10.1002/j.1552-4604.1981.tb05657.x. PMID   7037868. S2CID   19347859.
  7. ↑ Evans PJ, McQuay HJ, Rolfe M, O'Sullivan G, Bullingham RE, Moore RA (September 1982). "Zomepirac, placebo and paracetamol/dextropropoxyphene combination compared in orthopaedic postoperative pain". British Journal of Anaesthesia. 54 (9): 927–933. doi: 10.1093/bja/54.9.927 . PMID   7052110.
  8. ↑ 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. PMID   6991540. S2CID   7637029.
  9. ↑ 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. PMID   6991544. S2CID   45366160.
  10. ↑ Diamond S, Medina JL (March 1981). "A double-blind study of zomepirac sodium and placebo in the treatment of muscle contraction headache". Headache. 21 (2): 45–48. doi:10.1111/j.1526-4610.1981.hed2102045.x. PMID   7016809. S2CID   41806718.
  11. ↑ Wallenstein SL, Rogers A, Kaiko RF, Heidrich G, Houde RW (April 1980). "Relative analgesic potency of oral zomepirac and intramuscular morphine in cancer patients with postoperative pain". Journal of Clinical Pharmacology. 20 (4): 250–258. doi:10.1002/j.1552-4604.1980.tb01705.x. PMID   6991541. 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. ↑ Smith PC, McDonagh AF, Benet LZ (March 1986). "Irreversible binding of zomepirac to plasma protein in vitro and in vivo". The Journal of Clinical Investigation. 77 (3): 934–939. doi:10.1172/JCI112392. PMC   423485 . PMID   3949982.
  14. ↑ 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. 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
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.