Radafaxine

Radafaxine is described as a norepinephrine–dopamine reuptake inhibitor (NDRI). In contrast to bupropion, it appears to have a higher potency on inhibition of norepinephrine reuptake than on dopamine reuptake. Radafaxine has about 70% of the efficacy of bupropion in blocking dopamine reuptake, and 392% of efficacy in blocking norepinephrine reuptake, making it fairly selective for inhibiting the reuptake of norepinephrine over dopamine.{{cite journal | vauthors = Xu H, Loboz KK, Gross AS, McLachlan AJ | title = Stereoselective analysis of hydroxybupropion and application to drug interaction studies | journal = Chirality | volume = 19 | issue = 3 | pages = 163–70 | date = March 2007 | pmid = 17167747 | doi = 10.1002/chir.20356 }}{{cite journal | vauthors = Bondarev ML, Bondareva TS, Young R, Glennon RA | title = Behavioral and biochemical investigations of bupropion metabolites | journal = European Journal of Pharmacology | volume = 474 | issue = 1 | pages = 85–93 | date = August 2003 | pmid = 12909199 | doi = 10.1016/S0014-2999(03)02010-7 }} This, according to GlaxoSmithKline, may account for the increased effect of radafaxine on pain and fatigue.{{cite web | first = Daniel | last = Burch | name-list-style = vanc | title = Neurosciences Development Portfolio | url = http://213.219.8.102/pdfs/gsk/cns_seminar/353162.pdf | archive-url = https://web.archive.org/web/20070928035216/http://213.219.8.102/pdfs/gsk/cns_seminar/353162.pdf | archive-date = 2007-09-28 }} At least one study suggests that radafaxine has a low abuse potential similar to bupropion.{{cite journal | vauthors = Volkow ND, Wang GJ, Fowler JS, Learned-Coughlin S, Yang J, Logan J, Schlyer D, Gatley JS, Wong C, Zhu W, Pappas N, Schueller M, Jayne M, Carter P, Warner D, Ding YS, Shea C, Xu Y | display-authors = 6 | title = The slow and long-lasting blockade of dopamine transporters in human brain induced by the new antidepressant drug radafaxine predict poor reinforcing effects | journal = Biological Psychiatry | volume = 57 | issue = 6 | pages = 640–6 | date = March 2005 | pmid = 15780851 | doi = 10.1016/j.biopsych.2004.12.007 | s2cid = 13313064 }}

Radafaxine is a potent metabolite of bupropion, the compound in GlaxoSmithKline's Wellbutrin. More specifically, hydroxybupropion is a major metabolite of bupropion that is further metabolized via an intramolecular cyclization to give radafaxine as the (2S,3S) isomer,{{MeshName|Radafaxine}} as well as the corresponding (2R,3R) isomer isomer, which is less pharmacologically active as a monoamine reuptake inhibitor than radafaxine.{{cite journal | vauthors = Damaj MI, Carroll FI, Eaton JB, Navarro HA, Blough BE, Mirza S, Lukas RJ, Martin BR | title = Enantioselective effects of hydroxy metabolites of bupropion on behavior and on function of monoamine transporters and nicotinic receptors | journal = Mol Pharmacol | volume = 66 | issue = 3 | pages = 675–682 | date = September 2004 | pmid = 15322260 | doi = 10.1124/mol.104.001313 | url = }}{{cite journal | vauthors = Lukas RJ, Muresan AZ, Damaj MI, Blough BE, Huang X, Navarro HA, Mascarella SW, Eaton JB, Marxer-Miller SK, Carroll FI | title = Synthesis and characterization of in vitro and in vivo profiles of hydroxybupropion analogues: aids to smoking cessation | journal = J Med Chem | volume = 53 | issue = 12 | pages = 4731–4748 | date = June 2010 | pmid = 20509659 | pmc = 2895766 | doi = 10.1021/jm1003232 | url = }}{{cite journal | vauthors = Carroll FI, Muresan AZ, Blough BE, Navarro HA, Mascarella SW, Eaton JB, Huang X, Damaj MI, Lukas RJ | title = Synthesis of 2-(substituted phenyl)-3,5,5-trimethylmorpholine analogues and their effects on monoamine uptake, nicotinic acetylcholine receptor function, and behavioral effects of nicotine | journal = J Med Chem | volume = 54 | issue = 5 | pages = 1441–1448 | date = March 2011 | pmid = 21319801 | pmc = 3048909 | doi = 10.1021/jm1014555 | url = }} Manifaxine (GW-320,659) was developed as an analogue of radafaxine and has been studied for the treatment of ADHD and obesity.{{cite journal | vauthors = DeVeaugh-Geiss J, Conners CK, Sarkis EH, Winner PK, Ginsberg LD, Hemphill JM, Laurenza A, Barrows CE, Webster CJ, Stotka CJ, Asgharnejad M | display-authors = 6 | title = GW320659 for the treatment of attention-deficit/hyperactivity disorder in children | journal = Journal of the American Academy of Child and Adolescent Psychiatry | volume = 41 | issue = 8 | pages = 914–20 | date = August 2002 | doi = 10.1097/00004583-200208000-00009 | pmid = 12162627 }}{{cite journal | vauthors = Spraggs CF, Pillai SG, Dow D, Douglas C, McCarthy L, Manasco PK, Stubbins M, Roses AD | display-authors = 6 | title = Pharmacogenetics and obesity: common gene variants influence weight loss response of the norepinephrine/dopamine transporter inhibitor GW320659 in obese subjects | journal = Pharmacogenetics and Genomics | volume = 15 | issue = 12 | pages = 883–9 | date = December 2005 | doi = 10.1097/01213011-200512000-00006 | pmid = 16272960 | s2cid = 40809351 }}

• (2R,3R)-Hydroxybupropion
• 3-Chlorophenmetrazine
• Manifaxine

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Category:Abandoned drugs

Category:Alcohols

Category:Antidepressants

Category:Beta-Hydroxyamphetamines

Category:3-Chlorophenyl compounds

Category:Phenylmorpholines

Category:Nicotinic antagonists

Category:Norepinephrine–dopamine reuptake inhibitors