Radafaxine (developmental code name GW-353,162), also known as (2''S'',3''S'')-hydroxybupropion or (''S'',''S'')-hydroxybupropion, is a norepinephrine–dopamine reuptake inhibitor (NDRI) which was under development by

GlaxoSmithKline GSK plc, formerly GlaxoSmithKline plc, is a British Multinational corporation, multinational pharmaceutical and biotechnology company with global headquarters in London, England. Established in 2000 by a Mergers and acquisitions, merger of Gl ...

in the 2000s for a variety of different indications but was never marketed. These uses included treatment of

restless legs syndrome Restless legs syndrome (RLS), also known as Willis-Ekbom disease (WED), is generally a long-term disorder that causes a strong urge to move one's legs. There is often an unpleasant feeling in the legs that improves somewhat by moving them. This ...

major depressive disorder Major depressive disorder (MDD), also known as clinical depression, is a mental disorder characterized by at least two weeks of pervasive low mood, low self-esteem, and loss of interest or pleasure in normally enjoyable activities. Introdu ...

bipolar disorder Bipolar disorder, previously known as manic depression, is a mental disorder characterized by periods of depression and periods of abnormally elevated mood that last from days to weeks each. If the elevated mood is severe or associated with ...

neuropathic pain Neuropathic pain is pain caused by damage or disease affecting the somatosensory system. Neuropathic pain may be associated with abnormal sensations called dysesthesia or pain from normally non-painful stimuli ( allodynia). It may have continuo ...

fibromyalgia Fibromyalgia (FM) is a medical condition defined by the presence of chronic widespread pain, fatigue, waking unrefreshed, cognitive symptoms, lower abdominal pain or cramps, and depression. Other symptoms include insomnia and a general hype ...

, and

obesity Obesity is a medical condition, sometimes considered a disease, in which excess body fat has accumulated to such an extent that it may negatively affect health. People are classified as obese when their body mass index (BMI)—a person's ...

. Regulatory filing was planned for 2007, but development was discontinued in 2006 due to "poor test results".

Pharmacology

Pharmacodynamics

Radafaxine is described as a norepinephrine–dopamine reuptake inhibitor (NDRI). In contrast to bupropion, it appears to have a higher

potency Potency may refer to: * Potency (pharmacology), a measure of the activity of a drug in a biological system * Virility * Cell potency, a measure of the differentiation potential of stem cells * In homeopathic dilutions, potency is a measure of how ...

on inhibition of

norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad ...

reuptake than on

dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. Dopamine constitutes about 8 ...

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. This, according to GlaxoSmithKline, may account for the increased effect of radafaxine on

pain Pain is a distressing feeling often caused by intense or damaging stimuli. The International Association for the Study of Pain defines pain as "an unpleasant sensory and emotional experience associated with, or resembling that associated with, ...

and

fatigue Fatigue describes a state of tiredness that does not resolve with rest or sleep. In general usage, fatigue is synonymous with extreme tiredness or exhaustion that normally follows prolonged physical or mental activity. When it does not resolve ...

. At least one study suggests that radafaxine has a low

abuse potential Substance abuse, also known as drug abuse, is the use of a drug in amounts or by methods which are harmful to the individual or others. It is a form of substance-related disorder. Differing definitions of drug abuse are used in public health, ...

similar to bupropion.

Chemistry

Radafaxine is a potent

metabolite In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, ...

bupropion Bupropion, sold under the brand names Wellbutrin and Zyban among others, is an atypical antidepressant primarily used to treat major depressive disorder and to support smoking cessation. It is also popular as an add-on medication in the cas ...

, the compound in GlaxoSmithKline's

Wellbutrin Bupropion, sold under the brand names Wellbutrin and Zyban among others, is an atypical antidepressant primarily used to treat major depressive disorder and to support smoking cessation. It is also popular as an add-on medication in the cas ...

. More specifically, "

hydroxybupropion Hydroxybupropion (code name BW 306U), or 6-hydroxybupropion, is the major active metabolite of the antidepressant and smoking cessation drug bupropion. It is formed from bupropion by the liver enzyme CYP2B6 during first-pass metabolism. With oral ...

" is an analogue of bupropion, and radafaxine is an isolated isomer ((2''S'',3''S'')-) of hydroxybupropion. Therefore, radafaxine builds on at least some of the properties of bupropion in humans. Another analogue of bupropion,

manifaxine Manifaxine (developmental code name GW-320,659) is a norepinephrine–dopamine reuptake inhibitor developed by GlaxoSmithKline through structural modification of radafaxine, an isomer of hydroxybupropion and one of the active metabolites of b ...

(GW-320,659), was derived from radafxine and was also studied.

References

External links

* {{Nicotinic acetylcholine receptor modulators Abandoned drugs Alcohols Antidepressants Chloroarenes Substituted amphetamines Phenylethanolamines Phenylmorpholines Nicotinic antagonists Norepinephrine–dopamine reuptake inhibitors

Pharmacology

Pharmacodynamics

Chemistry

See also

References

External links