Radafaxine

drugbox
IUPAC_name = (+)-(2S,3S)-2-(3-chlorophenyl)-3,5,5-trimethylmorpholin-2-ol


width = 164
CAS_number = 106083-71-0
ATC_prefix =
ATC_suffix =
PubChem = 446
DrugBank =
C = 13 | H = 18 | Cl = 1 | N = 1 | O = 2
molecular_weight = 255.74 g/mol
bioavailability =
protein_bound =
metabolism =
elimination_half-life =
excretion =
pregnancy_AU =
pregnancy_US =
pregnancy_category=
legal_AU =
legal_CA =
legal_UK =
legal_US =
legal_status =
routes_of_administration =

Radafaxine is drug candidate designated 353162 [ [http://www.bioportfolio.com/reports/DMD_Restless%20Legs%20Syndrome%20First%20Approval.htm Restless Legs Syndrome: First Approval ] ] by GlaxoSmithKline, investigated for treatment of restless leg syndrome and as an NDRI antidepressant. GlaxoSmithKline was targeting Radafaxine for regulatory filing in 2007, [ [http://www.biospace.com/news_story.aspx?StoryID=18222420&full=1 {1} Reviews Novel Therapeutics For CNS Disorders And Confirms Strong Pipeline Momentum - News, Search Jobs, Events ] ] but development was discontinued in 2006 due to "poor test results". [ [http://news.independent.co.uk/business/news/article1199374.ece#10919204097707524565 GSK breakthrough on bird flu vaccine - Business News, Business - Independent.co.uk ] ]

Chemistry

It is a potent metabolite of bupropion, the compound in GlaxoSmithKline's Wellbutrin. More specifically, "hydroxybupropion" is a hydroxy derivative of bupropion, and radafaxine is an isolated isomer of hydroxybupropion. [MeshName|radafaxine]

Therefore, radafaxine builds on at least some of the properties of bupropion in humans. [ [http://www.prnewswire.com/cgi-bin/stories.pl?ACCT=105&STORY=/www/story/11-23-2004/0002499330 GlaxoSmithKline Reviews Novel Therapeutics for CNS Disorders and Confirms Strong Pipeline Momentum ] ]

Effects

Presently in various clinical trials, radafaxine is being 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 slightly 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. [ [http://213.219.8.102/pdfs/gsk/cns_seminar/353162.pdf Microsoft PowerPoint - slides_05_burch.ppt ] ]

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

At least one study suggests that radafaxine has a low abuse potential similar to bupropion. [ [http://www.biopsychiatry.com/radafaxine.htm Radafaxine ] ]

References