- Radafaxine
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IUPAC_name = (+)-(2S,3S)-2-(3-chlorophenyl)-3,5,5-trimethylmorpholin-2-ol
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CAS_number = 106083-71-0
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PubChem = 446
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C = 13 | H = 18 | Cl = 1 | N = 1 | O = 2
molecular_weight = 255.74 g/mol
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routes_of_administration =Radafaxine is
drug candidate designated 353162 [ [http://www.bioportfolio.com/reports/DMD_Restless%20Legs%20Syndrome%20First%20Approval.htm Restless Legs Syndrome: First Approval ] ] byGlaxoSmithKline , investigated for treatment ofrestless leg syndrome and as an NDRI antidepressant. GlaxoSmithKline was targeting Radafaxine for regulatory filing in 2007, [ [http://www.biospace.com/news_story.aspx?StoryID=18222420&full=1 {1} Reviews Novel Therapeutics For CNS Disorders And Confirms Strong Pipeline Momentum - News, Search Jobs, Events ] ] but development was discontinued in 2006 due to "poor test results". [ [http://news.independent.co.uk/business/news/article1199374.ece#10919204097707524565 GSK breakthrough on bird flu vaccine - Business News, Business - Independent.co.uk ] ]Chemistry
It is a potent metabolite of bupropion, the compound in GlaxoSmithKline's
Wellbutrin . More specifically, "hydroxybupropion" is ahydroxy derivative of bupropion, and radafaxine is an isolated isomer of hydroxybupropion. [MeshName|radafaxine]Therefore, radafaxine builds on at least some of the properties of bupropion in humans. [ [http://www.prnewswire.com/cgi-bin/stories.pl?ACCT=105&STORY=/www/story/11-23-2004/0002499330 GlaxoSmithKline Reviews Novel Therapeutics for CNS Disorders and Confirms Strong Pipeline Momentum ] ]
Effects
Presently in various
clinical trials , radafaxine is being studied as a treatment forclinical depression ,obesity , and neuropathic pain. Radafaxine is described as anorepinephrine-dopamine reuptake inhibitor (NDRI).Unlike
bupropion (which has a slightly higher effect ondopamine reuptake ), radafaxine seems to have a higher potency onnorepinephrine . This, according to GlaxoSmithKline, may account for the increased effect of radafaxine onpain and fatigue. [ [http://213.219.8.102/pdfs/gsk/cns_seminar/353162.pdf Microsoft PowerPoint - slides_05_burch.ppt ] ]Radafaxine has about 70% of bupropion's efficiacy in blocking dopamine reuptake, and 392% of efficiacy in blocking norepinephrine reuptake. [^ Xu H, Loboz KK, Gross AS, McLachlan AJ (2007). "Stereoselective analysis of hydroxybupropion and application to drug interaction studies". Chirality 19 (3): 163–70. doi:10.1002/chir.20356. PMID 17167747.] [ ^ Bondarev ML, Bondareva TS, Young R, Glennon RA (2003). "Behavioral and biochemical investigations of bupropion metabolites". Eur J Pharmacol 474 (1): 85–93. doi:10.1016/S0014-2999(03)02010-7. PMID 12909199. ]
At least one study suggests that radafaxine has a low abuse potential similar to bupropion. [ [http://www.biopsychiatry.com/radafaxine.htm Radafaxine ] ]
References
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