Radafaxine

Radafaxine

Systematic (IUPAC) name
(+)-(2S,3S)-2-(3-chlorophenyl)-3,5,5-trimethylmorpholin-2-ol
Identifiers
CAS Number	106083-71-0
ATC code	none
PubChem	CID 9795056
ChemSpider	7970823
UNII	Q47741214K
ChEMBL	CHEMBL1172928
Chemical data
Formula	C13H18ClNO2
Molar mass	292.20 g/mol
SMILES Clc1cccc(c1)[C@]2(O)OCC(N[C@H]2C)(C)C
InChI 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 Key:RCOBKSKAZMVBHT-TVQRCGJNSA-N
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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

It 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.^[4]

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

Effects

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. Radafaxine has about 70% of bupropion's efficacy in blocking dopamine reuptake, and 392% of efficacy in blocking norepinephrine reuptake, making it fairly selective for inhibiting the reuptake of norepinephrine over dopamine.^[6][7] This, according to GlaxoSmithKline, may account for the increased effect of radafaxine on pain and fatigue.^[8]

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

See also

• Manifaxine
• Phenmetrazine
• G-130
• 2-Phenyl-3,6-dimethylmorpholine

References

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. 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.
7. 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.
8. Microsoft PowerPoint - slides_05_burch.ppt
9. Radafaxine