| Revision as of 11:51, 20 February 2012 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Saving copy of the {{drugbox}} taken from revid 457134372 of page Zomepirac for the Chem/Drugbox validation project (updated: 'CAS_number'). |
Latest revision as of 17:42, 7 September 2024 edit JWBE (talk | contribs)Extended confirmed users10,111 edits removed Category:Chloroarenes; added Category:4-Chlorophenyl compounds using HotCat |
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{{Short description|Withdrawn non-steroidal anti-inflammatory drug}} |
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{{ambox | text = This page contains a copy of the infobox ({{tl|drugbox}}) taken from revid of page ] with values updated to verified values.}} |
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{{Drugbox |
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{{Drugbox |
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| Verifiedfields = changed |
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| Verifiedfields = changed |
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| Watchedfields = changed |
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| verifiedrevid = 416732999 |
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| verifiedrevid = 477869624 |
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| IUPAC_name = 2-acetic acid |
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| IUPAC_name = 2-acetic acid |
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| image = Zomepirac.png |
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| image = Zomepirac.svg |
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<!--Clinical data--> |
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<!--Clinical data--> |
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| tradename = |
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| tradename = |
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| legal_status = ''withdrawn'' |
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| legal_status = withdrawn |
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| routes_of_administration = oral |
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| routes_of_administration = ] |
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<!--Identifiers--> |
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<!--Identifiers--> |
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| CAS_number_Ref = {{cascite|correct|??}} |
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| CAS_number_Ref = {{cascite|changed|??}} |
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| CAS_number = <!-- blanked - oldvalue: 33369-31-2 --> |
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| CAS_number = 33369-31-2 |
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| ATC_prefix = M01 |
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| ATC_prefix = M01 |
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| ATC_suffix = AB04 |
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| ATC_suffix = AB04 |
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| PubChem = 5733 |
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| PubChem = 5733 |
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| DrugBank_Ref = {{drugbankcite|changed|drugbank}} |
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| DrugBank_Ref = {{drugbankcite|correct|drugbank}} |
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| DrugBank = DB04828 |
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| DrugBank = DB04828 |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| ChemSpiderID = 5531 |
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| ChemSpiderID = 5531 |
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| UNII_Ref = {{fdacite|changed|FDA}} |
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| UNII_Ref = {{fdacite|correct|FDA}} |
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| UNII = 822G987U9J |
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| UNII = 822G987U9J |
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| ChEBI_Ref = {{ebicite|changed|EBI}} |
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| ChEBI_Ref = {{ebicite|correct|EBI}} |
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| ChEBI = 35859 |
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| ChEBI = 35859 |
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| ChEMBL_Ref = {{ebicite|correct|EBI}} |
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| ChEMBL_Ref = {{ebicite|correct|EBI}} |
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<!--Chemical data--> |
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<!--Chemical data--> |
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| C=15 | H=14 | Cl=1 | N=1 | O=3 |
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| C=15 | H=14 | Cl=1 | N=1 | O=3 |
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| molecular_weight = 291.729 g/mol |
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| smiles = O=C(c1c(cc(n1C)CC(=O)O)C)c2ccc(Cl)cc2 |
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| smiles = O=C(c1c(cc(n1C)CC(=O)O)C)c2ccc(Cl)cc2 |
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| InChI = 1/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) |
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| InChIKey = ZXVNMYWKKDOREA-UHFFFAOYAX |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChI = 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) |
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| StdInChI = 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) |
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| StdInChIKey = ZXVNMYWKKDOREA-UHFFFAOYSA-N |
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| StdInChIKey = ZXVNMYWKKDOREA-UHFFFAOYSA-N |
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}} |
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}} |
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'''Zomepirac''' is an orally effective ] (NSAID) that has ] actions. It was developed by ], approved by the ] 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 ] in a small, but unpredictable, subset of the patient population.<ref>{{cite journal | author-link = Peter Rheinstein | vauthors = Rheinstein PH | url = http://www.findarticles.com/p/articles/mi_m3225/is_n3_v46/ai_12645044 | title = Reporting of adverse drug events: a key to postmarketing drug safety | journal = American Family Physician | date = September 1992 | volume = 46 | issue = 3 | pages = 873–874 | pmid = 1514478 }}</ref><ref>{{cite journal | vauthors = Grillo MP, Hua F | title = Identification of zomepirac-S-acyl-glutathione in vitro in incubations with rat hepatocytes and in vivo in rat bile | journal = Drug Metabolism and Disposition | volume = 31 | issue = 11 | pages = 1429–1436 | date = November 2003 | pmid = 14570776 | doi = 10.1124/dmd.31.11.1429 | s2cid = 9912756 }}</ref> |
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== Indications == |
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Zomepirac was indicated for the management of mild to severe pain.<ref name="JAMA">{{cite journal | vauthors = Lewis JR | title = Zomepirac sodium. A new nonaddicting analgesic | journal = JAMA | volume = 246 | issue = 4 | pages = 377–379 | year = 1981 | pmid = 7241789 | doi = 10.1001/jama.246.4.377 }}</ref> Multiple clinical trials demonstrated zomepirac to be more effective than ] or ] alone and to be as effective as analgesic combinations containing codeine or other ]s.<ref>{{cite journal | vauthors = Steele CE, Jefferson WL | title = A multi-centre study of zomepirac in painful conditions: an analysis of clinical data for 15,484 patients | journal = Current Medical Research and Opinion | volume = 8 | issue = 6 | pages = 382–391 | year = 1983 | pmid = 6221886 | doi = 10.1185/03007998309111743 }}</ref><ref>{{cite journal | vauthors = Mehlisch DR, Joy ED | title = Zomepirac sodium vs APC with codeine for oral surgery pain | journal = Journal of Oral Surgery | volume = 39 | issue = 6 | pages = 426–429 | date = June 1981 | pmid = 7014804 }}</ref><ref>{{cite journal | vauthors = Stambaugh JE, Sarajian C | title = Analgesic efficacy of zomepirac sodium in patients with pain due to cancer | journal = Journal of Clinical Pharmacology | volume = 21 | issue = 11 | pages = 501–507 | year = 1981 | pmid = 7037868 | doi = 10.1002/j.1552-4604.1981.tb05657.x | s2cid = 19347859 }}</ref><ref>{{cite journal | vauthors = Evans PJ, McQuay HJ, Rolfe M, O'Sullivan G, Bullingham RE, Moore RA | title = Zomepirac, placebo and paracetamol/dextropropoxyphene combination compared in orthopaedic postoperative pain | journal = British Journal of Anaesthesia | volume = 54 | issue = 9 | pages = 927–933 | date = September 1982 | pmid = 7052110 | doi = 10.1093/bja/54.9.927 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Baird WM, Turek D | title = Comparison of zomepirac, APC with codeine, codeine and placebo in the treatment of moderate and severe postoperative pain | journal = Journal of Clinical Pharmacology | volume = 20 | issue = 4 | pages = 243–249 | date = April 1980 | pmid = 6991540 | doi = 10.1002/j.1552-4604.1980.tb01704.x | s2cid = 7637029 }}</ref><ref>{{cite journal | vauthors = Mehlisch DR, Joy ED, Moore TE, Porter K, Stumpf AJ, Wolfe SH | title = Clinical comparison of zomepirac with APC/codeine combination in the treatment of pain following oral surgery | journal = Journal of Clinical Pharmacology | volume = 20 | issue = 4 | pages = 271–278 | date = April 1980 | pmid = 6991544 | doi = 10.1002/j.1552-4604.1980.tb01708.x | s2cid = 45366160 }}</ref><ref>{{cite journal | vauthors = Diamond S, Medina JL | title = A double-blind study of zomepirac sodium and placebo in the treatment of muscle contraction headache | journal = Headache | volume = 21 | issue = 2 | pages = 45–48 | date = March 1981 | pmid = 7016809 | doi = 10.1111/j.1526-4610.1981.hed2102045.x | s2cid = 41806718 }}</ref> Zomepirac provided analgesia comparable with usual ] doses of ] in postoperative pain and that with long-term use, neither ] to its analgesic effect nor psychological or ] had been demonstrated.<ref name="JAMA" /><ref>{{cite journal | vauthors = Wallenstein SL, Rogers A, Kaiko RF, Heidrich G, Houde RW | title = Relative analgesic potency of oral zomepirac and intramuscular morphine in cancer patients with postoperative pain | journal = Journal of Clinical Pharmacology | volume = 20 | issue = 4 | pages = 250–258 | date = April 1980 | pmid = 6991541 | doi = 10.1002/j.1552-4604.1980.tb01705.x | s2cid = 11808742 }}</ref> |
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== Chemical structure == |
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Zomepirac is the sodium salt of 5-(4-chlorobenzoyl)-1,4 dimethyl-1''H''-pyrrole-2-acetate dihydrate. It is a ]-] which is structurally related to ]. The chemical structure differs from other NSAIDs in that the central benzene ring has been replaced by a pyrrole. |
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== Mechanism of action == |
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Zomepirac is a ] ].<ref>DC McLeod, {{webarchive |url=https://web.archive.org/web/20070928041224/http://www.theannals.com/cgi/content/abstract/15/7/522 |date=September 28, 2007 }}, ''Drug Intelligence & Clinical Pharmacy'': Vol. 15, No. 7, pp. 522-530.</ref> |
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== Anaphylaxis == |
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Zomepirac does not cause anaphylaxis directly, but it is metabolized by ] (UGT) to a reactive ] which binds irreversibly to plasma ].<ref name="Smith1986">{{cite journal | vauthors = Smith PC, McDonagh AF, Benet LZ | title = Irreversible binding of zomepirac to plasma protein in vitro and in vivo | journal = The Journal of Clinical Investigation | volume = 77 | issue = 3 | pages = 934–939 | date = March 1986 | pmid = 3949982 | pmc = 423485 | doi = 10.1172/JCI112392 | author3-link = Leslie Z. Benet }}</ref> |
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== Synthesis == |
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Zomepirac can be synthesized from diethyl 1,3-acetonedicarboxylate, ], and aqueous ] (MeNH<sub>2</sub>) via modification of the ] to give intermediate '''1'''. Saponification, monoesterification, and thermal decarboxylation gives ester '''2'''. This is acylated with ''N'',''N''-dimethyl-''p''-chlorobenzamide, and finally ] gives zomepirac ('''3'''). |
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|assign=]|inventor = Carson JR }}</ref><ref>{{cite patent | inventor = Carson JS | country = US | number = 3752826 | gdate = 1973 | assign1 = ] }}</ref>]]{{clear left}} |
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== See also == |
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* ] |
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* ] |
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== References == |
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{{Reflist}} |
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{{Anti-inflammatory and antirheumatic products}} |
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{{Prostanoidergics}} |
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] |
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] |
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] |
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] |
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] |
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] |