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 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. Intro ...
,
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 continuous ...
,
fibromyalgia, 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 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 and
fatigue. 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 of
bupropion, 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 case ...
. 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 ora ...
" 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 bup ...
(GW-320,659), was derived from radafxine and was also studied.
See also
*
3-Chlorophenmetrazine
*
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 bup ...
References
External links
*
{{Nicotinic acetylcholine receptor modulators
Abandoned drugs
Alcohols
Antidepressants
Chloroarenes
Substituted amphetamines
Phenylethanolamines
Phenylmorpholines
Nicotinic antagonists
Norepinephrine–dopamine reuptake inhibitors