Chemical compound
Identifiers |
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CAS Number | - 192374-14-4 Y
- HCl: 106083-71-0 Y
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PubChem CID | |
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ChemSpider | - 7970823 Y
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UNII | - Q47741214K
- HCl: SYD411HZ3S Y
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ChEMBL | - ChEMBL1172928 Y
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Chemical and physical data |
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Formula | C13H18ClNO2 |
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Molar mass | 255.74 g·mol−1 |
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3D model (JSmol) | |
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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 YKey:RCOBKSKAZMVBHT-TVQRCGJNSA-N Y |
NY (what is this?) (verify) |
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]
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 radafaxine and was also studied.[10]
See also
References
- ^ Carroll FI, Blough BE, Mascarella SW, Navarro HA, Lukas RJ, Damaj MI (2014). "Bupropion and Bupropion Analogs as Treatments for CNS Disorders". Emerging Targets & Therapeutics in the Treatment of Psychostimulant Abuse. Advances in Pharmacology. Vol. 69. pp. 177–216. doi:10.1016/B978-0-12-420118-7.00005-6. ISBN 9780124201187. PMID 24484978.
- ^ a b "Radafaxine - AdisInsight".
- ^ a b "Reviews Novel Therapeutics For CNS Disorders And Confirms Strong Pipeline Momentum". BioSpace. 23 November 2004. Archived from the original on 2007-09-28.
- ^ Kollewe J (27 July 2006). "GSK breakthrough on bird flu vaccine". Independent.co.uk. Archived from the original on 2007-10-01.
- ^ 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.
- ^ 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.
- ^ Burch D. "Neurosciences Development Portfolio" (PDF). Archived from the original (PDF) on 2007-09-28.
- ^ 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.
- ^ Radafaxine at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- ^ "Manifaxine - AdisInsight".
External links
- Media related to Radafaxine at Wikimedia Commons
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SSRIsTooltip Selective serotonin reuptake inhibitors | |
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SNRIsTooltip Serotonin–norepinephrine reuptake inhibitors | |
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NRIsTooltip Norepinephrine reuptake inhibitors | |
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NDRIsTooltip Norepinephrine–dopamine reuptake inhibitors | |
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NaSSAsTooltip Noradrenergic and specific serotonergic antidepressants | |
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SARIsTooltip Serotonin antagonist and reuptake inhibitors | |
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SMSTooltip Serotonin modulator and stimulators | |
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TCAsTooltip Tricyclic antidepressants | |
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TeCAsTooltip Tetracyclic antidepressants | |
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Others | |
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Non-selective | |
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MAOATooltip Monoamine oxidase A-selective | |
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MAOBTooltip Monoamine oxidase B-selective | |
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DATTooltip Dopamine transporter (DRIsTooltip Dopamine reuptake inhibitors) | |
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NETTooltip Norepinephrine transporter (NRIsTooltip Norepinephrine reuptake inhibitors) | | | | | | | - Others: Antihistamines (e.g., brompheniramine, chlorphenamine, pheniramine, tripelennamine)
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SERTTooltip Serotonin transporter (SRIsTooltip Serotonin reuptake inhibitors) | | | | | - Others: A-80426
- Amoxapine
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- Roxindole
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VMATsTooltip Vesicular monoamine transporters | |
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Others | |
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See also: Receptor/signaling modulators • Monoamine releasing agents • Adrenergics • Dopaminergics • Serotonergics • Monoamine metabolism modulators • Monoamine neurotoxins |
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nAChRsTooltip Nicotinic acetylcholine receptors | Agonists (and PAMsTooltip positive allosteric modulators) | - 5-HIAA
- 6-Chloronicotine
- A-84,543
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Antagonists (and NAMsTooltip negative allosteric modulators) | |
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Precursors (and prodrugs) | |
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- See also
- Receptor/signaling modulators
- Muscarinic acetylcholine receptor modulators
- Acetylcholine metabolism/transport modulators
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