| 词条 | Medifoxamine |
| 释义 |
| verifiedrevid = 444759950 | IUPAC_name = N,N-dimethyl-2,2-diphenoxyethanamine | image = Medifoxamine Structural Formulae.png | width = 200px | tradename = Clédial, Gerdaxyl | pregnancy_category = | legal_status = Rx-only | routes_of_administration = By mouth | bioavailability = 21%[1][2] | metabolism = | elimination_half-life = 2.8 hours (acute);[1][2] 4.0 hours (chronic)[3] | excretion = | CAS_number_Ref = {{cascite|correct|??}} | CAS_number = 32359-34-5 | CAS_supplemental = 16604-45-8 (fumarate) 16604-44-7 (picrate) | ATC_prefix = N06 | ATC_suffix = AX13 | PubChem = 36109 | ChemSpiderID = 33212 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = KWU7C2A1NT | KEGG_Ref = {{keggcite|correct|kegg}} | KEGG = D07341 | synonyms = Medifoxamine fumarate; N,N-Dimethyl-2,2-diphenoxyethylamine | C=16 | H=19 | N=1 | O=2 | molecular_weight = 257.328 g/mol | SMILES = CN(C)CC(OC1=CC=CC=C1)OC2=CC=CC=C2 | StdInChI = 1S/C16H19NO2/c1-17(2)13-16(18-14-9-5-3-6-10-14)19-15-11-7-4-8-12-15/h3-12,16H,13H2,1-2H3 | StdInChIKey = QNMGHBMGNRQPNL-UHFFFAOYSA-N | chirality = Racemic mixture }}Medifoxamine, previously sold under the brand names Clédial and Gerdaxyl, is an atypical antidepressant[4] with additional anxiolytic properties[5] acting via dopaminergic and serotonergic mechanisms which was formerly marketed in France and Spain, as well as Morocco.[6][7][8][9][10] The drug was first introduced in France sometime around 1990.[11] It was withdrawn from the market in 1999 (Morocco) and 2000 (France) following incidences of hepatotoxicity.[10][12][13]{{TOC limit|3}} PharmacologyPharmacodynamicsMedifoxamine has been found to act preferentially as a relatively weak dopamine reuptake inhibitor,[3][14][15][16] but also as an even weaker serotonin reuptake inhibitor (IC50 = 1,500 nM)[3] and as a weak antagonist of the 5-HT2A and 5-HT2C receptors (IC50 = 950 and 980, respectively; notably greater affinity relative to amitriptyline and imipramine).[3][17][18] It is known to produce two active metabolites during first-pass metabolism in the liver, CRE-10086 (N-methyl-2,2-diphenoxyethylamine) and CRE-10357 (N,N-dimethyl-2-hydroxyphenoxy-2-phenoxyethylamine).[3] The IC50 values of CRE-10086 for serotonin transporter, 5-HT2A, and 5-HT2C binding are 450 nM, 330 nM, and 700 nM, respectively, while those of CRE-10357 are 660 nM, 1,600 nM, and 6,300 M.[3] Medifoxamine and its metabolites lack affinity for other serotonin receptors including 5-HT1A, 5-HT1B, 5-HT1D, and 5-HT3 (>10,000 nM).[3] As medifoxamine is metabolized extensively in the liver during first-pass metabolism, and as these metabolites have as much as 3-fold greater activity relative to medifoxamine, it is likely that they contribute significantly to the pharmacology of the parent drug.[3] Effectiveness and tolerabilityUnlike many tricyclic antidepressants, medifoxamine lacks anticholinergic and alpha blocker properties (very low affinity for the muscarinic acetylcholine receptors and 10-fold lower affinity for the α1-adrenergic receptor relative to 5-HT2 binding sites),[3][14][19] and is also apparently inactive as a norepinephrine reuptake inhibitor (although the same source stating this also states that it is inactive as a serotonin reuptake inhibitor, which was subsequently found not to be the case).[20] Studies in mice revealed that the drug does not possess any sedative or locomotor stimulant effects.[3] In accordance with all of the preceding, medifoxamine was found to be well-tolerated at dosages of 100–300 mg per day in clinical trials.[3] Double-blind controlled clinical studies have found it to have similar effectiveness to imipramine, clomipramine, and maprotiline in the treatment of depression.[3][9][18][19] Society and cultureGeneric namesMedifoxamine is the generic name of the drug and its {{abbrlink|INN|International Nonproprietary Name}} while médifoxamine is its {{abbrlink|DCF|Dénomination Commune Française}}.[6][7][8]Brand namesMedifoxamine was marketed under the brand names Clédial and Gerdaxyl.[6][7] References1. ^1 {{cite journal|last1=Saleh|first1=S|last2=Johnston|first2=A|last3=Turner|first3=P|title=Absolute bioavailability and pharmacokinetics of medifoxamine in healthy humans.|journal=British Journal of Clinical Pharmacology|volume=30|issue=4|year=1990|pages=621–624|issn=0306-5251|doi=10.1111/j.1365-2125.1990.tb03823.x|pmc=1368255}} {{Antidepressants}}{{Monoamine reuptake inhibitors}}{{Serotonin receptor modulators}}2. ^1 {{cite book|author=Florencio Zaragoza Dörwald|title=Lead Optimization for Medicinal Chemists: Pharmacokinetic Properties of Functional Groups and Organic Compounds|url=https://books.google.com/books?id=YTeY9ZEfNccC&pg=PA259|date=4 February 2013|publisher=John Wiley & Sons|isbn=978-3-527-64565-7|pages=259–}} 3. ^1 2 3 4 5 6 7 8 9 10 11 {{cite journal | vauthors = Gainsborough N, Nelson ML, Maskrey V, Swift CG, Jackson SH | title = The pharmacokinetics and pharmacodynamics of medifoxamine after oral administration in healthy elderly volunteers | journal = Eur. J. Clin. Pharmacol. | volume = 46 | issue = 2 | pages = 163–6 | year = 1994 | pmid = 8039537 | doi = 10.1007/bf00199882| url = }} 4. ^{{cite book|author1=Jayna Holroyd-Leduc|author2=Madhuri Reddy|title=Evidence-Based Geriatric Medicine|url=https://books.google.com/books?id=VfPIUfcwrFkC&pg=PT299|date=9 March 2012|publisher=John Wiley & Sons|isbn=978-1-118-28181-9|pages=299–}} 5. ^{{cite book|title=ANNUAL REPORTS IN MED CHEMISTRY V22 PPR|url=https://books.google.com/books?id=oJeTSJveeuAC&pg=PA323|date=2 September 1987|publisher=Academic Press|isbn=978-0-08-058366-2|pages=323–}} 6. ^1 2 {{cite book|author=J. Elks|title=The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies|url=https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA759|date=14 November 2014|publisher=Springer|isbn=978-1-4757-2085-3|pages=759–}} 7. ^1 2 {{cite book|title=Index Nominum 2000: International Drug Directory|url=https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA638|date=January 2000|publisher=Taylor & Francis|isbn=978-3-88763-075-1|pages=638–}} 8. ^1 {{cite book|author1=I.K. Morton|author2=Judith M. Hall|title=Concise Dictionary of Pharmacological Agents: Properties and Synonyms|url=https://books.google.com/books?id=mqaOMOtk61IC&pg=PA173|date=31 October 1999|publisher=Springer Science & Business Media|isbn=978-0-7514-0499-9|pages=173–}} 9. ^1 {{cite journal | vauthors = Mitchell PB | title = Novel French antidepressants not available in the United States | journal = Psychopharmacol Bull | volume = 31 | issue = 3 | pages = 509–19 | year = 1995 | pmid = 8668756 | doi = | url = }} 10. ^1 {{cite book|title=Consolidated List of Products Whose Consumption And/or Sale Have Been Banned, Withdrawn, Severely Restricted Or Not Approved by Governments|url=https://books.google.com/books?id=leVCukUgNlsC&pg=PA135|year=2003|publisher=United Nations Publications|isbn=978-92-1-130230-1|pages=135–136}} 11. ^{{cite journal | vauthors = Saleh S, Johnston A, Edeki T, Turner P | title = Tolerability and kinetics of intravenous medifoxamine in healthy volunteers | journal = Int Clin Psychopharmacol | volume = 5 | issue = 2 | pages = 97–102 | year = 1990 | pmid = 2380545 | doi = 10.1097/00004850-199004000-00003| url = }} 12. ^{{cite journal | vauthors = Dumortier G, Cabaret W, Stamatiadis L, Saba G, Benadhira R, Rocamora JF, Aubriot-Delmas B, Glikman J, Januel D | title = [Hepatic tolerance of atypical antipsychotic drugs] | language = French | journal = Encephale | volume = 28 | issue = 6 Pt 1 | pages = 542–51 | year = 2002 | pmid = 12506267 | doi = | url = }} 13. ^{{cite book|author1=George I. Papakostas|author2=Maurizio Fava|title=Pharmacotherapy for Depression and Treatment-resistant Depression|url=https://books.google.com/books?id=zigp-66vq0MC&pg=PA88|year=2010|publisher=World Scientific|isbn=978-981-4287-59-3|pages=88–}} 14. ^1 {{cite journal|last1=Saleh|first1=S|last2=Turner|first2=P|title=Ocular hypotensive effects of medifoxamine.|journal=British Journal of Clinical Pharmacology|volume=34|issue=3|year=1992|pages=269–271|issn=0306-5251|doi=10.1111/j.1365-2125.1992.tb04136.x|pmc=1381400}} 15. ^{{cite journal|last1=Vaugeois|first1=J.-M.|last2=Pouhé|first2=D.|last3=Lemonnier|first3=F.|last4=Costentin|first4=J.|title=Neurochemical and behavioral evidence for a central indirect dopaminergic agonist activity of the antidepressant medifoxamine in mice|journal=European Neuropsychopharmacology|volume=4|issue=3|year=1994|pages=323–324|issn=0924-977X|doi=10.1016/0924-977X(94)90140-6}} 16. ^{{cite journal|last1=Berk|first1=Michael|title=Depression therapy: Future prospects|journal=International Journal of Psychiatry in Clinical Practice|volume=4|issue=4|year=2000|pages=281–286|issn=1365-1501|doi=10.1080/13651500050517830}} 17. ^{{cite journal | vauthors = Martin P, Lemonnier F | title = [The role of type 2 serotonin receptors, 5-HT2A and 5-HT2C, in depressive disorders: effect of medifoxamine] | language = French | journal = Encephale | volume = 20 | issue = 4 | pages = 427–35 | year = 1994 | pmid = 7988407 | doi = | url = }} 18. ^1 {{cite journal | vauthors = Olié JP, Galinowski A, Lehert P, Lemonnier F, Lôo H | title = [Randomized double-blind comparative study of the efficacy and tolerance of medifoxamine and imipramine in depressed patients] | language = French | journal = Encephale | volume = 19 | issue = 4 | pages = 333–40 | year = 1993 | pmid = 8275921 | doi = | url = }} 19. ^1 {{cite journal|last1=Randhawa|first1=M. A.|last2=Hedges|first2=A.|last3=Johnston|first3=A.|last4=Turner|first4=P.|title=A psychopharmacological study to assess anti-muscarinic and central nervous effects of medifoxamine in normal volunteers|journal=Human Psychopharmacology: Clinical and Experimental|volume=3|issue=3|year=1988|pages=195–200|issn=0885-6222|doi=10.1002/hup.470030307}} 20. ^{{cite book|title=ANNUAL REPORTS IN MED CHEMISTRY V20 PPR|url=https://books.google.com/books?id=j-3Cd_SWIksC&pg=PA35|date=11 September 1985|publisher=Academic Press|isbn=978-0-08-058364-8|pages=35–}} 9 : 5-HT2A antagonists|5-HT2C antagonists|Amines|Anxiolytics|Bicyclic antidepressants|Hepatotoxins|Phenol ethers|Serotonin-dopamine reuptake inhibitors|Withdrawn drugs |
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