| 词条 | Nefopam | ||||||||||||||
| 释义 |
| Verifiedfields = changed | Watchedfields = changed | verifiedrevid = 445783136 | IUPAC_name = (RS)-5-methyl-1-phenyl-1,3,4,6-tetrahydro-2,5-benzoxazocine | image = Nefopam2DACS.svg | width = 135px | image2 = File:Nefopam ball-and-stick model.png | width2 = 150px | tradename = néfopam medisol | Drugs.com = {{drugs.com|international|nefopam}} | pregnancy_category = | legal_AU = S4 | legal_UK = POM | routes_of_administration = Oral, intramuscular, intravenous | bioavailability = Low[1] | protein_bound = 70–75% (mean 73%)[1][2] | metabolism = Liver (N-demethylation, others)[1] | metabolites = Desmethylnefopam, others[1] | elimination_half-life = Nefopam: 3–8 hours[1] Desmethylnefopam: 10–15 hours[1] | excretion = Urine: 79.3%[1] Feces: 13.4%[1] | CAS_number_Ref = {{cascite|correct|??}} | CAS_number = 13669-70-0 | ATC_prefix = N02 | ATC_suffix = BG06 | PubChem = 4450 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = 4UP8060B7J | KEGG_Ref = {{keggcite|correct|kegg}} | KEGG = D08258 | ChEBI_Ref = {{ebicite|changed|EBI}} | ChEBI = 88316 | ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}} | ChemSpiderID = 4295 | synonyms = | C=17 | H=19 | N=1 | O=1 | molecular_weight = 253.34 g/mol | SMILES = CN1CCOC(C2=CC=CC=C2C1)C3=CC=CC=C3 | StdInChI_Ref = {{stdinchicite|changed|chemspider}} | StdInChI = 1S/C17H19NO/c1-18-11-12-19-17(14-7-3-2-4-8-14)16-10-6-5-9-15(16)13-18/h2-10,17H,11-13H2,1H3 | StdInChIKey_Ref = {{stdinchicite|changed|chemspider}} | StdInChIKey = RGPDEAGGEXEMMM-UHFFFAOYSA-N }}Nefopam, sold under the brand names Acupan and nefopam medisol among others, is a painkilling medication. It is primarily used to treat moderate to severe, acute or chronic pain.[3] It is believed to work in the brain and spinal cord to relieve pain. There it is believed to work via unique mechanisms. Firstly it increases the activity of the serotonin, norepinephrine and dopamine, neurotransmitters involved in, among other things, pain signaling. Secondly, it modulates sodium and calcium channels, thereby inhibiting the release of glutamate, a key neurotransmitter involved in pain processing.[11] Medical usesNefopam is effective for prevention of shivering during surgery or recovery from surgery.[4][5] Nefopam was significantly more effective than aspirin as an analgesic in one clinical trial,[6] although with a greater incidence of side effects such as sweating, dizziness and nausea, especially at higher doses.[7][8] The estimated relative potency of nefopam to morphine indicates that 20 mg of nefopam HCl is the approximate analgesic equal of 12 mg of morphine with comparable analgesic efficacy to morphine,[9][10][11] or oxycodone,[12] while Nefopam tends to produce fewer side effects, does not produce respiratory depression,[13] and has much less abuse potential, and so is useful either as an alternative to opioids, or as an adjunctive treatment for use alongside opioid(s) or other analgesics.[11][14] Nefopam is also used to treat severe hiccups.[15] Desmoid tumorsNefopam is being studied as a treatment for the desmoid tumors associated with aggressive fibromatosis.[16] Nefopam has been shown to slow or stop desmoid tumors' growth in mice during a pre-clinical phase study.[17] ContraindicationsNefopam is contraindicated in people with convulsive disorders, those that have received treatment with irreversible monoamine oxidase inhibitors such as phenelzine, tranylcypromine or isocarboxazid within the past 30 days and those with myocardial infarction pain, mostly due to a lack of safety data in these conditions.[27] Side effectsCommon side effects include nausea, nervousness, dry mouth, light-headedness and urinary retention.[18] Less common side effects include vomiting, blurred vision, drowsiness, sweating, insomnia, headache, confusion, hallucinations, tachycardia, aggravation of angina and rarely a temporary and benign pink discolouration of the skin or erythema multiforme.[18] Overall, the incidence of side-effects are less with the oral formulation and generally transient and mild in nature. OverdoseOverdose and death have been reported with nefopam,[19] although these events are less common with nefopam than with opioid analgesics.[20] Overdose usually manifests with convulsions, hallucinations, tachycardia, and hyperdynamic circulation.[18] Treatment is usually supportive, managing cardiovascular complications with beta blockers and limiting absorption with activated charcoal.[18]InteractionsIt has additive anticholinergic and sympathomimetic effects with other agents with these properties.[18] Its use should be avoided in people receiving some types of antidepressants (tricyclic antidepressants or monoamine oxidase inhibitors) as there is the potential for serotonin syndrome or hypertensive crises to result.[18] Pharmacology
The mechanism of action of nefopam and its analgesic effects are not well understood, although inhibition of the reuptake of serotonin, norepinephrine, and to a lesser extent dopamine (that is, acting as an {{abbrlink|SNDRI|serotonin–norepinephrine–dopamine reuptake inhibitor}}) is thought to be involved.[23][11] It also reduces glutamate signaling via modulating sodium and calcium channels.[24][25] PharmacokineticsThe absolute bioavailability of nefopam is low.[1] It is reported to achieve therapeutic plasma concentrations between 49 and 183 nM.[22] The drug is approximately 73% protein-bound across a plasma range of 7 to 226 ng/mL (28–892 nM).[1] The metabolism of nefopam is hepatic, by N-demethylation and via other routes.[1] Its terminal half-life is 3 to 8 hours, while that of its active metabolite, desmethylnefopam, is 10 to 15 hours.[1] It is eliminated mostly in urine, and to a lesser extent in feces.[1] ChemistryNefopam is a cyclized analogue of orphenadrine, diphenhydramine, and tofenacin, with each of these compounds different from one another only by the presence of one or two carbons.[26][27][28] The ring system of nefopam is a benzoxazocine system.[26][29] Society and cultureRecreational useRecreational use of nefopam has rarely been reported,[19] and is far less common than with opioid analgesics.[20] References1. ^1 2 3 4 5 6 7 8 9 10 11 12 {{cite journal | vauthors = Sanga M, Banach J, Ledvina A, Modi NB, Mittur A | title = Pharmacokinetics, metabolism, and excretion of nefopam, a dual reuptake inhibitor in healthy male volunteers | journal = Xenobiotica; The Fate of Foreign Compounds in Biological Systems | volume = 46 | issue = 11 | pages = 1001–16 | date = November 2016 | pmid = 26796604 | doi = 10.3109/00498254.2015.1136989 }} {{Analgesics}}{{Navboxes2. ^{{cite book| vauthors = Seyffart G |title=Drug Dosage in Renal Insufficiency|url=https://books.google.com/books?id=OavnCAAAQBAJ&pg=PA407|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-94-011-3804-8|pages=407–}} 3. ^{{cite web|title=Nefopam hydrochloride|website=MedicinesComplete|publisher=Pharmaceutical Press|editor=Brayfield, A|url=https://www.medicinescomplete.com/mc/martindale/current/2674-m.htm|location=London, UK|date=27 October 2016|access-date=4 September 2017}} 4. ^{{cite journal |vauthors=Kang P, Park SK, Yoo S, Hur M, Kim WH, Kim JT, Bahk JH |title=Comparative effectiveness of pharmacologic interventions to prevent shivering after surgery: a network meta-analysis |journal=Minerva Anestesiol |volume=85 |issue=1 |pages=60–70 |date=January 2019 |pmid=30226340 |doi=10.23736/S0375-9393.18.12813-6 |url=}} 5. ^{{cite journal | vauthors = Alfonsi P, Adam F, Passard A, Guignard B, Sessler DI, Chauvin M | title = Nefopam, a nonsedative benzoxazocine analgesic, selectively reduces the shivering threshold in unanesthetized subjects | journal = Anesthesiology | volume = 100 | issue = 1 | pages = 37–43 | date = January 2004 | pmid = 14695722 | pmc = 1283107 | doi = 10.1097/00000542-200401000-00010 }} 6. ^{{cite journal | vauthors = Cohen A, Hernandez CM | title = Nefopam hydrochloride: new analgesic agent | journal = The Journal of International Medical Research | volume = 4 | issue = 2 | pages = 138–43 | year = 1976 | pmid = 799984 | doi = 10.1177/030006057600400211 }} 7. ^{{cite journal | vauthors = Wang RI, Waite EM | title = The clinical analgesic efficacy of oral nefopam hydrochloride | journal = Journal of Clinical Pharmacology | volume = 19 | issue = 7 | pages = 395–402 | date = July 1979 | pmid = 479385 | doi = 10.1002/j.1552-4604.1979.tb02498.x }} 8. ^{{cite journal | vauthors = Pillans PI, Woods DJ | title = Adverse reactions associated with nefopam | journal = The New Zealand Medical Journal | volume = 108 | issue = 1008 | pages = 382–4 | date = September 1995 | pmid = 7566787 }} 9. ^{{cite journal | vauthors = Sunshine A, Laska E | title = Nefopam and morphine in man | journal = Clinical Pharmacology and Therapeutics | volume = 18 | issue = 5 Pt 1 | pages = 530–4 | date = November 1975 | pmid = 1102231 | doi = 10.1002/cpt1975185part1530 }} 10. ^{{cite journal | vauthors = Phillips G, Vickers MD | title = Nefopam in postoperative pain | journal = British Journal of Anaesthesia | volume = 51 | issue = 10 | pages = 961–5 | date = October 1979 | pmid = 391253 | doi = 10.1093/bja/51.10.961 }} 11. ^1 {{cite journal | vauthors = Heel RC, Brogden RN, Pakes GE, Speight TM, Avery GS | title = Nefopam: a review of its pharmacological properties and therapeutic efficacy | journal = Drugs | volume = 19 | issue = 4 | pages = 249–67 | date = April 1980 | pmid = 6991238 | doi = 10.2165/00003495-198019040-00001 }} 12. ^{{cite journal | vauthors = Tigerstedt I, Tammisto T, Leander P | title = Comparison of the analgesic dose-effect relationships of nefopam and oxycodone in postoperative pain | journal = Acta Anaesthesiologica Scandinavica | volume = 23 | issue = 6 | pages = 555–60 | date = December 1979 | pmid = 397711 | doi = 10.1111/j.1399-6576.1979.tb01486.x }} 13. ^{{cite journal | vauthors = Gasser JC, Bellville JW | title = Respiratory effects of nefopam | journal = Clinical Pharmacology and Therapeutics | volume = 18 | issue = 2 | pages = 175–9 | date = August 1975 | pmid = 1097153 | doi = 10.1002/cpt1975182175 }} 14. ^{{cite journal | vauthors = Kapfer B, Alfonsi P, Guignard B, Sessler DI, Chauvin M | title = Nefopam and ketamine comparably enhance postoperative analgesia | journal = Anesthesia and Analgesia | volume = 100 | issue = 1 | pages = 169–74 | date = January 2005 | pmid = 15616073 | pmc = 1283103 | doi = 10.1213/01.ANE.0000138037.19757.ED }} 15. ^{{cite journal | vauthors = Bilotta F, Rosa G | title = Nefopam for severe hiccups | journal = The New England Journal of Medicine | volume = 343 | issue = 26 | pages = 1973–4 | date = December 2000 | pmid = 11186682 | doi = 10.1056/nejm200012283432619 }} 16. ^{{cite journal | vauthors = Poon R, Hong H, Wei X, Pan J, Alman BA | title = A high throughput screen identifies Nefopam as targeting cell proliferation in β-catenin driven neoplastic and reactive fibroproliferative disorders | journal = PLOS One | volume = 7 | issue = 5 | pages = e37940 | date = 2012 | pmid = 22666417 | pmc = 3364163 | doi = 10.1371/journal.pone.0037940 }} 17. ^{{Cite news|url=https://dtrf.org/dtrfs-groundbreaking-project/|title=DTRF's Groundbreaking Project - Desmoid Tumor Research Foundation|work=Desmoid Tumor Research Foundation|access-date=2018-11-28|language=en-US}} 18. ^1 2 3 4 5 6 {{cite web|title=Data Sheet ACUPAN™ Nefopam hydrochloride 30 mg tablets 20 mg intramuscular injection|work=Medsafe New Zealand|publisher=iNova Pharmaceuticals (New Zealand) Limited|date=3 September 2007|url=http://www.medsafe.govt.nz/profs/datasheet/a/acupantabinj.pdf|format=PDF|access-date=10 March 2014}} 19. ^1 {{cite journal | vauthors = Bismuth C, Fournier PE, Bavoux E, Husson O, Lafon D | title = [Chronic abuse of the analgesic nefopam (Acupan)] | language = French | journal = Journal De Toxicologie Clinique Et Experimentale | volume = 7 | issue = 5 | pages = 343–6 | date = September 1987 | pmid = 3448182 }} 20. ^1 {{cite journal | vauthors = Tracqui A, Berthelon L, Ludes B | title = Fatal overdosage with nefopam (Acupan) | journal = Journal of Analytical Toxicology | volume = 26 | issue = 4 | pages = 239–43 | date = May 2002 | pmid = 12054367 | doi = 10.1093/jat/26.4.239 | url = http://jat.oxfordjournals.org/content/26/4/239.full.pdf | format = PDF }} 21. ^{{cite web | title = PDSP Ki Database | work = Psychoactive Drug Screening Program (PDSP) | author1 = Roth, BL | author2 = Driscol, J | publisher = University of North Carolina at Chapel Hill and the United States National Institute of Mental Health | access-date = 14 August 2017 | url = https://kidbdev.med.unc.edu/databases/pdsp.php?knowID=0&kiKey=&receptorDD=&receptor=&speciesDD=&species=&sourcesDD=&source=&hotLigandDD=&hotLigand=&testLigandDD=&testFreeRadio=testFreeRadio&testLigand=nefopam&referenceDD=&reference=&KiGreater=&KiLess=&kiAllRadio=all&doQuery=Submit+Query}} 22. ^1 {{cite journal | vauthors = Gregori-Puigjané E, Setola V, Hert J, Crews BA, Irwin JJ, Lounkine E, Marnett L, Roth BL, Shoichet BK | title = Identifying mechanism-of-action targets for drugs and probes | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 109 | issue = 28 | pages = 11178–83 | date = July 2012 | pmid = 22711801 | pmc = 3396511 | doi = 10.1073/pnas.1204524109 | url = http://www.pnas.org/content/early/2012/06/12/1204524109.full.pdf | format = PDF }} 23. ^{{cite web|author=Bausch & Lomb (NZ) Ltd|title=NEW ZEALAND DATA SHEET ACUPAN(TM)|url=http://www.medsafe.govt.nz/profs/Datasheet/a/acupantabinj.pdf|publisher=New Zealand The Ministry of Health|website=Medsafe|date=17 May 2017|access-date=4 September 2017|format=PDF}} 24. ^{{cite journal | vauthors = Kim KH, Abdi S | title = Rediscovery of nefopam for the treatment of neuropathic pain | journal = The Korean Journal of Pain | volume = 27 | issue = 2 | pages = 103–11 | date = April 2014 | pmid = 24748937 | pmc = 3990817 | doi = 10.3344/kjp.2014.27.2.103 }} 25. ^1 2 {{cite journal | vauthors = Girard P, Chauvin M, Verleye M | title = Nefopam analgesia and its role in multimodal analgesia: A review of preclinical and clinical studies | journal = Clinical and Experimental Pharmacology & Physiology | volume = 43 | issue = 1 | pages = 3–12 | date = January 2016 | pmid = 26475417 | doi = 10.1111/1440-1681.12506 }} 26. ^1 {{cite book| first1 = Camille Georges | last1 = Wermuth | first2 = David | last2 = Aldous | first3 = Pierre | last3 = Raboisson | first4 = Didier | last4 = Rognan | name-list-format = vanc |title=The Practice of Medicinal Chemistry|url=https://books.google.com/books?id=dtScBAAAQBAJ&pg=PA250|date=1 July 2015|publisher=Elsevier Science|isbn=978-0-12-417213-5|pages=250–251}} 27. ^{{cite book| first = Walter | last = Sneader | name-list-format = vanc |title=Drug Discovery: A History|url=https://books.google.com/books?id=Cb6BOkj9fK4C&pg=PA405|date=23 June 2005|publisher=John Wiley & Sons|isbn=978-0-471-89979-2|pages=405–}} 28. ^{{cite book| first1 = Hugo | last1 = Kubinyi | first2 = Gerhard | last2 = Müller | name-list-format = vanc |title=Chemogenomics in Drug Discovery: A Medicinal Chemistry Perspective|url=https://books.google.com/books?id=oxvYXJSCImUC&pg=PA54|date=6 March 2006|publisher=John Wiley & Sons|isbn=978-3-527-60402-9|pages=54–}} 29. ^{{cite book| first = Amy | last = Cruz | name-list-format = vanc |title=Therapeutic Hypothermia|url=https://books.google.com/books?id=lpETxii5bjQC&pg=PA176|year=2014|publisher=CRC Press|pages=176– }} | title = Pharmacodynamics | titlestyle = background:#ccccff | list1 ={{Ion channel modulators}}{{Monoamine reuptake inhibitors}}{{Muscarinic acetylcholine receptor modulators}}{{Serotonin receptor modulators}} }} 8 : Analgesics|Antidepressants|Drugs with unknown mechanisms of action|Muscarinic antagonists|Nitrogen heterocycles|Oxygen heterocycles|Serotonin-norepinephrine-dopamine reuptake inhibitors|Sodium channel blockers |
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