Radafaxine Explained

Radafaxine (developmental code GW-353,162; also known as (2S,3S)-hydroxybupropion or (S,S)-hydroxybupropion[1]) is a norepinephrine–dopamine reuptake inhibitor (NDRI) which was under development by GlaxoSmithKline in the 2000s for a variety of different indications but was never marketed.[2] These uses included treatment of restless legs syndrome, major depressive disorder, bipolar disorder, neuropathic pain, fibromyalgia, and obesity. Regulatory filing was planned for 2007,[3] but development was discontinued in 2006 due to "poor test results".[4]

Pharmacology

Pharmacodynamics

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.[5] [6] This, according to GlaxoSmithKline, may account for the increased effect of radafaxine on pain and fatigue.[7] At least one study suggests that radafaxine has a low abuse potential similar to bupropion.[8]

Chemistry

Radafaxine is a potent metabolite of bupropion, the compound in GlaxoSmithKline's Wellbutrin. More specifically, "hydroxybupropion" is an analogue of bupropion, and radafaxine is an isolated isomer ((2S,3S)-) of hydroxybupropion. Therefore, radafaxine builds on at least some of the properties of bupropion in humans. Another analogue of bupropion, manifaxine (GW-320,659), was derived from radafaxine and was also studied.[9]

See also

Notes and References

  1. Book: Carroll FI, Blough BE, Mascarella SW, Navarro HA, Lukas RJ, Damaj MI . Bupropion and Bupropion Analogs as Treatments for CNS Disorders . Emerging Targets & Therapeutics in the Treatment of Psychostimulant Abuse . Advances in Pharmacology . 69 . 177–216 . 2014 . 24484978 . 10.1016/B978-0-12-420118-7.00005-6 . 9780124201187 .
  2. Web site: Radafaxine - AdisInsight.
  3. Web site: Reviews Novel Therapeutics For CNS Disorders And Confirms Strong Pipeline Momentum . BioSpace . 23 November 2004 . https://web.archive.org/web/20070928041150/http://www.biospace.com/news_story.aspx?StoryID=18222420&full=1 . 2007-09-28 .
  4. Web site: Julia . Kollewe . vanc . 27 July 2006 . Independent.co.uk . GSK breakthrough on bird flu vaccine . dead . https://web.archive.org/web/20071001051510/http://news.independent.co.uk/business/news/article1199374.ece . 2007-10-01 .
  5. Xu H, Loboz KK, Gross AS, McLachlan AJ . Stereoselective analysis of hydroxybupropion and application to drug interaction studies . Chirality . 19 . 3 . 163–70 . March 2007 . 17167747 . 10.1002/chir.20356 .
  6. Bondarev ML, Bondareva TS, Young R, Glennon RA . Behavioral and biochemical investigations of bupropion metabolites . European Journal of Pharmacology . 474 . 1 . 85–93 . August 2003 . 12909199 . 10.1016/S0014-2999(03)02010-7 .
  7. Web site: Daniel . Burch . vanc . Neurosciences Development Portfolio . https://web.archive.org/web/20070928035216/http://213.219.8.102/pdfs/gsk/cns_seminar/353162.pdf . 2007-09-28 .
  8. 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 . 6 . The slow and long-lasting blockade of dopamine transporters in human brain induced by the new antidepressant drug radafaxine predict poor reinforcing effects . Biological Psychiatry . 57 . 6 . 640–6 . March 2005 . 15780851 . 10.1016/j.biopsych.2004.12.007 . 13313064 .
  9. Web site: Manifaxine - AdisInsight.

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