Radafaxine

Radafaxine (developmental code name 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]

Radafaxine
Clinical data
Other names(S,S)-Hydroxybupropion; (2S,3S)-Hydroxybupropion; GW-353,162
Routes of
administration		Oral
ATC code
  • none
Identifiers
  • (+)-(2S,3S)-2-(3-chlorophenyl)-3,5,5-trimethylmorpholin-2-ol
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
Chemical and physical data
FormulaC13H18ClNO2
Molar mass255.74 g·mol−1
3D model (JSmol)
  • Clc1cccc(c1)[C@]2(O)OCC(N[C@H]2C)(C)C
  • InChI=1S/C13H18ClNO2/c1-9-13(16,17-8-12(2,3)15-9)10-5-4-6-11(14)7-10/h4-7,9,15-16H,8H2,1-3H3/t9-,13+/m0/s1 Y
  • Key:RCOBKSKAZMVBHT-TVQRCGJNSA-N Y
 NY (what is this?)  (verify)

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 radafxine and was also studied.[10]

See also

References
  1. Carroll FI, Blough BE, Mascarella SW, Navarro HA, Lukas RJ, Damaj MI (2014). Bupropion and bupropion analogs as treatments for CNS disorders. Adv Pharmacol. Advances in Pharmacology. 69. pp. 177–216. doi:10.1016/B978-0-12-420118-7.00005-6. ISBN 9780124201187. PMID 24484978.
  2. https://adisinsight.springer.com/drugs/800017221
  3. "Reviews Novel Therapeutics For CNS Disorders And Confirms Strong Pipeline Momentum". BioSpace. 23 November 2004. Archived from the original on 2007-09-28.
  4. Kollewe J (27 July 2006). "GSK breakthrough on bird flu vaccine". Independent.co.uk. Archived from the original on 2007-10-01.
  5. 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.
  6. 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.
  7. Burch D. "Neurosciences Development Portfolio" (PDF). Archived from the original (PDF) on 2007-09-28.
  8. 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.
  9. Radafaxine at the US National Library of Medicine Medical Subject Headings (MeSH)
  10. https://adisinsight.springer.com/drugs/800006906


This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.