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| Other names | (S,S)-Hydroxybupropion; (2S,3S)-Hydroxybupropion; GW-353,162 |
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Routes of administration | Oral |
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| Formula | C13H18ClNO2 |
| Molar mass | 255.74 g·mol−1 |
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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. [2] 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. [9] Therefore, radafaxine builds on at least some of the properties of bupropion in humans. [3] Another analogue of bupropion, manifaxine (GW-320,659), was derived from radafaxine and was also studied. [10]
See also
References
- ^ Carroll FI, Blough BE, Mascarella SW, Navarro HA, Lukas RJ, Damaj MI (2014). "Bupropion and Bupropion Analogs as Treatments for CNS Disorders". Emerging Targets & Therapeutics in the Treatment of Psychostimulant Abuse. Advances in Pharmacology. Vol. 69. pp. 177–216. doi: 10.1016/B978-0-12-420118-7.00005-6. ISBN 9780124201187. PMID 24484978.
- ^ a b "Radafaxine - AdisInsight".
- ^ a b "Reviews Novel Therapeutics For CNS Disorders And Confirms Strong Pipeline Momentum". BioSpace. 23 November 2004. Archived from the original on 2007-09-28.
- ^ Kollewe J (27 July 2006). "GSK breakthrough on bird flu vaccine". Independent.co.uk. Archived from the original on 2007-10-01.
- ^ Xu H, Loboz KK, Gross AS, McLachlan AJ (March 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 (August 2003). "Behavioral and biochemical investigations of bupropion metabolites". European Journal of Pharmacology. 474 (1): 85–93. doi: 10.1016/S0014-2999(03)02010-7. PMID 12909199.
- ^ Burch D. "Neurosciences Development Portfolio" (PDF). Archived from the original (PDF) on 2007-09-28.
- ^ Volkow ND, Wang GJ, Fowler JS, Learned-Coughlin S, Yang J, Logan J, et al. (March 2005). "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. doi: 10.1016/j.biopsych.2004.12.007. PMID 15780851. S2CID 13313064.
- ^ Radafaxine at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- ^ "Manifaxine - AdisInsight".
External links
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Media related to
Radafaxine at Wikimedia Commons
