Radafaxine

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Radafaxine
Radafaxine Structural Formulae.png
Systematic (IUPAC) name
(+)-(2S,3S)-2-(3-chlorophenyl)-3,5,5-trimethylmorpholin-2-ol
Clinical data
Legal status?
Identifiers
CAS number106083-71-0 N
ATC codeNone
PubChemCID 9795056
ChemSpider7970823 YesY
UNIIQ47741214K YesY
ChEMBLCHEMBL1172928 YesY
Chemical data
FormulaC13H18ClNO2 
Mol. mass292.20 g/mol
 N (what is this?)  (verify)
 
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Radafaxine
Radafaxine Structural Formulae.png
Systematic (IUPAC) name
(+)-(2S,3S)-2-(3-chlorophenyl)-3,5,5-trimethylmorpholin-2-ol
Clinical data
Legal status?
Identifiers
CAS number106083-71-0 N
ATC codeNone
PubChemCID 9795056
ChemSpider7970823 YesY
UNIIQ47741214K YesY
ChEMBLCHEMBL1172928 YesY
Chemical data
FormulaC13H18ClNO2 
Mol. mass292.20 g/mol
 N (what is this?)  (verify)

Radafaxine is drug candidate designated GW-353,162[1] by GlaxoSmithKline, investigated for treatment of restless leg syndrome and as an NDRI antidepressant. GlaxoSmithKline was targeting Radafaxine for regulatory filing in 2007,[2] but development was discontinued in 2006 due to "poor test results".[3]

Chemistry[edit]

It is a potent metabolite of bupropion, the compound in GlaxoSmithKline's Wellbutrin. More specifically, "6-hydroxybupropion" is an analogue of bupropion, and radafaxine is an isolated isomer of 6-hydroxybupropion.[4]

Therefore, radafaxine builds on at least some of the properties of bupropion in humans.[5]

Effects[edit]

In various clinical trials, radafaxine has been studied as a treatment for clinical depression, obesity, and neuropathic pain. Radafaxine is described as a norepinephrine-dopamine reuptake inhibitor (NDRI).

Unlike bupropion (which has a much higher effect on dopamine reuptake), radafaxine seems to have a higher potency on norepinephrine. This, according to GlaxoSmithKline, may account for the increased effect of radafaxine on pain and fatigue.[6]

Radafaxine has about 70% of bupropion's efficacy in blocking dopamine reuptake, and 392% of efficacy in blocking norepinephrine reuptake.[7][8]

At least one study suggests that radafaxine has a low abuse potential similar to bupropion.[9]

See also[edit]

References[edit]

  1. ^ Restless Legs Syndrome: First Approval
  2. ^ {1} Reviews Novel Therapeutics For CNS Disorders And Confirms Strong Pipeline Momentum - News, Search Jobs, Events
  3. ^ Independent.co.uk: GSK breakthrough on bird flu vaccine.
  4. ^ radafaxine at the US National Library of Medicine Medical Subject Headings (MeSH)
  5. ^ GlaxoSmithKline Reviews Novel Therapeutics for CNS Disorders and Confirms Strong Pipeline Momentum
  6. ^ Microsoft PowerPoint - slides_05_burch.ppt
  7. ^ 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. 
  8. ^ 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. 
  9. ^ Radafaxine