Radafaxine
Chemical compound
From Wikipedia, the free encyclopedia
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]
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| Other names | (S,S)-Hydroxybupropion; (2S,3S)-Hydroxybupropion; GW-353,162 |
| Routes of administration | Oral |
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| Formula | C13H18ClNO2 |
| Molar mass | 255.74 g·mol−1 |
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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 a major metabolite of bupropion that is further metabolized via an intramolecular cyclization to give radafaxine as the (2S,3S) isomer,[9] as well as the corresponding (2R,3R) isomer isomer, which is less pharmacologically active as a monoamine reuptake inhibitor than radafaxine.[10][11][12] Manifaxine (GW-320,659) was developed as an analogue of radafaxine and has been studied for the treatment of ADHD and obesity.[13][14]
