Examine individual changes

'{{drugbox | verifiedrevid = 464372587 | IUPAC_name = (+)-(''S'')-2-(6-methoxynaphthalen-2-yl)<br />propanoic acid | image = Naproxen2.svg | image2= Naproxen3d.png | width = 240 | CASNo_Ref = {{cascite|correct|CAS}} | UNII_Ref = {{fdacite|correct|FDA}} | UNII = 57Y76R9ATQ | InChI = 1/C14H14O3/c1-9(14(15)16)10-3-4-12-8-13(17-2)6-5-11(12)7-10/h3-9H,1-2H3,(H,15,16)/t9-/m0/s1 | InChIKey = CMWTZPSULFXXJA-VIFPVBQEBN | smiles = C[C@@H](c1ccc2cc(ccc2c1)OC)C(=O)O | ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL = 154 | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 1S/C14H14O3/c1-9(14(15)16)10-3-4-12-8-13(17-2)6-5-11(12)7-10/h3-9H,1-2H3,(H,15,16)/t9-/m0/s1 | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = CMWTZPSULFXXJA-VIFPVBQESA-N | CAS_number_Ref = {{cascite|correct|??}} | CAS_number = 22204-53-1 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 137720 | ATC_prefix = G02 | ATC_suffix = CC02 | ATC_supplemental = {{ATC|M01|AE02}}, {{ATC|M02|AA12}} | ChEBI_Ref = {{ebicite|correct|EBI}} | ChEBI = 7476 | PubChem = 156391 | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank = DB00788 | KEGG_Ref = {{keggcite|correct|kegg}} | KEGG = D00118 | C = 14 |H = 14 |O = 3 | molecular_weight = 230.259 [[Gram|g]]/[[Mole (unit)|mol]] | bioavailability = 95% (oral) | protein_bound = 99% | metabolism = [[Hepatic]] (to 6-desmethylnaproxen) | elimination_half-life = 12–24 hours | excretion = [[Renal]] | pregnancy_AU = C | pregnancy_US = C | pregnancy_category = | legal_AU = S2 | legal_UK = P | legal_US = OTC | legal_status = OTC<small>([[Canada|Ca]])</small> | routes_of_your_mom = Your Grandparents | tradename = Aleve | Drugs.com = {{drugs.com|monograph|naproxen}} | MedlinePlus = a681029 | license_US = naproxen | DailyMedID= 43871 }} '''Naproxen sodium''' ([[International Nonproprietary Name|INN]]) {{IPAc-en|n|ə|ˈ|p|r|ɒ|k|s|ən}} is a [[nonsteroidal anti-inflammatory drug]] (NSAID) and is commonly used for relief of a wide variety of pain, fever, inflammations, and stiffness. == Medical uses == Naproxen is commonly used for the reduction of [[pain]], [[fever]], [[inflammation]] and stiffness caused by conditions including [[migraine]], [[osteoarthritis]], [[kidney stones]], [[rheumatoid arthritis]], [[psoriatic arthritis]], [[gout]], [[ankylosing spondylitis]], [[menstrual cramp]]s, [[tendinitis]] and [[bursitis]]. It is also used for the treatment of primary [[dysmenorrhea]].<ref name="pmid15686299">{{cite journal | author = French L | title = Dysmenorrhea | journal = [[Am Fam Physician]] | volume = 71 | issue = 2 | pages = 285–91 | year = 2005 | pmid = 15686299 | url = http://www.aafp.org/afp/2005/0115/p285.pdf }}</ref> ===Diagnostics=== Naproxen has been utilized to differentiate between infectious [[fever]]s and those with [[neoplastic]] or [[connective tissue disease]] related fevers.<ref>{{cite journal|author=Dy, Emmanuel Edwin R. et al. |url=http://www.psmid.org.ph/vol28/vol28num3topic2.pdf |title=The Naproxen Test as a Diagnostic Tool in the Causative Differentiation of Fever|journal=Philipp J Intern Med |year=1996 |volume=34|issue=6|pages=235–239}}</ref><ref>{{cite journal|author=Zell JA, Chang JC|title= Neoplastic fever: a neglected paraneoplastic syndrome|pmid= 15864658|year=2005|volume=13|issue=11|pages=870–7|doi=10.1007/s00520-005-0825-4|journal=Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer}}</ref> ==Adverse effects== [[COX-2]] selective and nonselective [[NSAIDs]] have been linked to increases in the number of serious and potentially fatal cardiovascular events, such as [[myocardial infarctions]] and [[stroke]]s. Naproxen is however associated with the smallest overall cardiovascular risks.<ref name = Trelle>{{cite journal | journal = [[BMJ]] | year = 2011 | volume = 342 | title = Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis | author = Trelle S, Reichenbach S, Wandel S, Hildebrand P, Tschannen B, Villiger PM, Egger M, Jüni P. | doi = 10.1136/bmj.c7086 | id = c7086 | pmid=21224324 |pmc=3019238| pages = c7086 }}</ref><ref name=j1>{{cite journal|author=Coxib and traditional NSAID Trialists' (CNT) Collaboration, Bhala N, Emberson J, Merhi A, Abramson S, Arber N, Baron JA, Bombardier C, Cannon C, Farkouh ME, FitzGerald GA, Goss P, Halls H, Hawk E, Hawkey C, Hennekens C, Hochberg M, Holland LE, Kearney PM, Laine L, Lanas A, Lance P, Laupacis A, Oates J, Patrono C, Schnitzer TJ, Solomon S, Tugwell P, Wilson K, Wittes J, Baigent C|title=Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials|journal=Lancet|date=2013|volume=382|issue=9894|pages=769–79|pmid=23726390|doi=10.1016/S0140-6736(13)60900-9|displayauthors=30}}</ref> The drug had roughly 50% of the associated risk of stroke as compared with [[ibuprofen]] and was also associated with a reduced number of myocardial infarctions as compared to control groups.<ref name=Trelle/> As with other non-COX-2 selective NSAIDs, naproxen can cause [[gastrointestinal]] problems, such as heartburn, constipation, diarrhea, ulcers and stomach bleeding.<ref>[http://web.archive.org/web/20100722112536/http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0000526 Naproxen]. PubMed Health.</ref> Persons with a history of [[ulcers]] or [[inflammatory bowel disease]] should consult a doctor before taking naproxen. It was found that high-dose naproxen induced near-complete suppression of platelet [[thromboxane]] throughout the dosing interval and appeared not to increase cardiovascular disease (CVD) risk, whereas other high-dose NSAID regimens had only transient effects on platelet [[COX-1]] and were associated "with a small but definite vascular hazard". Conversely, naproxen was associated with higher rates of upper gastrointestinal bleeding complications in comparison to other NSAIDs.<ref name=j1/> NSAID painkillers, such as naproxen, may interfere with and reduce the efficacy of [[SSRI]] antidepressants.<ref>Tudor, Amy (2011-04-20) [http://www.healthcentral.com/depression/treatment-579181-5.html Why Painkillers Interfere with Anti-depressants]. Healthcentral.com. Retrieved on 2013-09-20.</ref><ref name="pmid21518864">{{cite journal | author = Warner-Schmidt JL | coauthors = Vanover KE; Chen EY; Marshall JJ; Greengard P | title = Antidepressant effects of selective serotonin reuptake inhibitors (SSRIs) are attenuated by antiinflammatory drugs in mice and humans | journal = [[Proc. Natl. Acad. Sci. U.S.A.]] | volume = 108 | issue = 22 | pages = 9262–7 | year = 2011 | pmid = 21518864 | pmc = 3107316 | doi = 10.1073/pnas.1104836108}}</ref> ==Mechanism of action== Naproxen works by inhibiting both the [[PTGS1|COX-1]] and [[Prostaglandin-endoperoxide synthase 2|COX-2]] [[enzymes]].<ref>{{cite journal|author=Duggan KC, Walters MJ, Musee J, Harp JM, Kiefer JR, Oates JA, Marnett LJ|pmid=20810665|year=2010|title=Molecular basis for cyclooxygenase inhibition by the non-steroidal anti-inflammatory drug naproxen|volume=285|issue=45|pages=34950–9|doi=10.1074/jbc.M110.162982|pmc=2966109|journal=The Journal of biological chemistry}}</ref><ref>{{cite journal|author=Hinz B, Cheremina O, Besz D, Zlotnick S, Brune K.|pmid=18397691|year=2008|title=Impact of naproxen sodium at over-the-counter doses on cyclooxygenase isoforms in human volunteers|volume=46|issue=4|pages=180–6|journal=International journal of clinical pharmacology and therapeutics|doi=10.5414/CPP46180}}</ref><ref>{{cite journal|author=Van Hecken A, Schwartz JI, Depré M, De Lepeleire I, Dallob A, Tanaka W, Wynants K, Buntinx A, Arnout J, Wong PH, Ebel DL, Gertz BJ, De Schepper PJ|pmid=11028250|year=2000|title=Comparative inhibitory activity of rofecoxib, meloxicam, diclofenac, ibuprofen, and naproxen on COX-2 versus COX-1 in healthy volunteers|volume=40|issue=10|pages=1109–20|journal=Journal of clinical pharmacology}}</ref><ref>{{cite journal|author=Gross GJ, Moore J. |pmid=15161995|year=2004|title=Effect of COX-1/COX-2 inhibition versus selective COX-2 inhibition on coronary vasodilator responses to arachidonic acid and acetylcholine|volume=71|issue=3|pages=135–42|doi=10.1159/000077447|journal=Pharmacology}}</ref><ref>{{cite journal|author=Hawkey CJ|pmid=11566042|year=2001|title=COX-1 and COX-2 inhibitors|volume=15|issue=5|pages=801–20|doi=10.1053/bega.2001.0236|journal=Best practice & research. Clinical gastroenterology}}</ref> == Compound information == {{unreferenced section|date=May 2012}} Naproxen is a member of the 2-arylpropionic acid (profen) family of NSAIDs. The free acid is an odorless, white to off-white, crystalline substance. It is [[lipid]]-soluble and practically insoluble in water. It has a [[melting point]] of 152–155 [[Celsius|°C]]. ==Synthesis== Naproxen has been industrially produced by Syntex as follows:<ref name = Harrington>{{cite journal | journal = [[Org. Process Res. Dev.]] | year = 1997 | volume = 1 | issue = 1 | pages = 72–76 | title = Twenty Years of Naproxen Technology | author = Peter J. Harrington and Eric Lodewijk | doi = 10.1021/op960009e}}</ref> :[[File:Large-Scale Synthesis of S-naproxen.png|500px]] Other synthetic routes have also been discussed.<ref name = Harrington/> ==Marketing and trade names== Naproxen and naproxen sodium are marketed under various trade names, including: Aleve, Anaprox, Antalgin, Apranax, Feminax Ultra, Flanax, Inza, Midol Extended Relief, Nalgesin, Naposin, Naprelan, Naprogesic, Naprosyn, Narocin, Proxen, Soproxen, Synflex and Xenobid. Naproxen was originally marketed as the [[prescription drug]] Naprosyn by [[Syntex]] in 1976, and naproxen sodium was first marketed under the trade name Anaprox in 1980. It remains a prescription-only drug in much of the world. In the United States, the [[Food and Drug Administration]] (FDA) approved its use as an [[Over-the-counter drug|over-the-counter (OTC) drug]] in 1994; OTC preparations in the U.S. are mainly marketed by [[Bayer USA|Bayer HealthCare]] under the trade name Aleve and generic [[store brand]] formulations in 220&nbsp;mg tablets. In Australia, packets of 275&nbsp;mg tablets of naproxen sodium are [[Standard for the Uniform Scheduling of Drugs and Poisons#Schedule 2 Pharmacy Medicine|Schedule 2 pharmacy medicines]], with a maximum daily dose of five tablets or 1375&nbsp;mg. In the United Kingdom, 250-mg tablets of naproxen were approved for OTC sale under the brand name Feminax Ultra in 2008, for the treatment of primary [[dysmenorrhoea]] in women aged 15 to 50.<ref>{{cite press release | date = 1 April 2008 | title=Medicines regulator approves availability of a new OTC medicine for period pain | url = http://www.mhra.gov.uk/home/idcplg?IdcService=GET_FILE&dDocName=CON014482&RevisionSelectionMethod=LatestReleased | format = PDF | publisher = Medicines and Healthcare products Regulatory Agency (MHRA) }}</ref> In the Netherlands, 220mg and 275mg tablets are available OTC in drugstores, 550mg is OTC only at pharmacists. Aleve became available over-the-counter in most provinces in Canada on 14 July 2009, but not [[British Columbia]], [[Quebec]] or [[Newfoundland and Labrador]];<ref>{{cite press release|url=http://www.bayer.ca/files/Aleve%20Release.July14.FINAL_.pdf|title=ALEVE – Welcome to Canada, Eh!|date=14 July 2009|publisher=Bayer Health Care|accessdate=24 March 2012}}</ref> it became available OTC in [[British Columbia]] in late January 2010.<ref name="Press Release, January 2010">{{cite web|title=ALEVE® – Helping British Columbians with Joint and Arthritis Pain Get Back to Doing the Activities They Love|url=http://www.newswire.ca/en/story/703499/aleve-r-helping-british-columbians-with-joint-and-arthritis-pain-get-back-to-doing-the-activities-they-love|work=newswire.ca|date=28 January 2010}}</ref> ==Research== Naproxen may have anti-viral activity against [[influenza]]. Specifically, it blocks the RNA-binding groove of the nucleoprotein of the virus, thereby preventing formation of the ribonucleoprotein complex, thus taking the vital nucleoproteins out of circulation.<ref>[http://www.eurekalert.org/pub_releases/2013-03/asfm-prs032113.phpPain reliever shows anti-viral activity against flu]. Eurekalert.org (2013-03-21). Retrieved on 2013-09-20.</ref><ref>{{Cite doi|10.1128/AAC.02335-12}}</ref> ==References== {{Reflist|30em}} ==External links== {{Wiktionary|naproxen}} * {{Official website|http://www.aleve.com/|name=Aleve U.S.}} * {{Official website|http://www.aleve.ca/|name=Aleve Canada}} * {{PubChemLink|1302}} * {{EINECSLink|244-838-7}} * [http://www.nlm.nih.gov/medlineplus/druginfo/meds/a681029.html MedlinePlus Information on naproxen] * [http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2004/ucm108387.htm FDA Statement on Naproxen], released 20 December 2004 * [http://www.clinicaltrials.gov/show/NCT00007189 Alzheimer's Disease Anti-Inflammatory Prevention Trial] * [http://archive.is/20130123133555/http://www.forbes.com/2005/02/18/cx_mh_0218naproxen.html Forbes article] (expressing the point of view that the risk of heart attack or stroke was overstated) * [http://www.medscape.com/viewarticle/703957 Which NSAID for Heart Disease Patients? – Medscape] * [http://druginfo.nlm.nih.gov/drugportal/dpdirect.jsp?name=Naproxen U.S. National Library of Medicine: Drug Information Portal – Naproxen] * [http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=2247e68f-60ba-42fc-b617-2fc2843994a5 Aleve] Daily Med * [http://www.ebi.ac.uk/pdbe-srv/PDBeXplore/ligand/?ligand=NPX Naproxen bound to proteins] in the [[Protein Data Bank|PDB]] * [http://www.what-is-rsd.com/medication.html Use of naproxen in the Treatment of RSD] * [http://www.mjlphd.net/1/post/2013/10/testing-of-our-new-polarimeter.html] (Chemistry blog describing the extraction and testing of enantiomeric purity of naproxen sodium purchased at [[Dollar Tree]]) {{Anti-inflammatory and antirheumatic products}} {{Topical products for joint and muscular pain}} {{Analgesics}} {{Prolactin inhibitors and anti-inflammatory products for vaginal administration}} [[Category:Analgesics]] [[Category:Antipyretics]] [[Category:Equine medications]] [[Category:Naphthol ethers]] [[Category:Non-steroidal anti-inflammatory drugs]] [[Category:Propionic acids]]'