Delving into the Latest Updates on Radafaxine Hydrochloride with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Bupropion metabolite, Radafaxine, Radafaxine hydrochloride (USAN)

+ [4]

Target

DAT x adrenergic receptor x nAChR α4/β2/α5

Mechanism

DAT antagonists(Dopamine transporter antagonists), Nicotinic acetylcholine receptor alpha4/beta2/alpha5 antagonists, adrenergic receptor antagonists(Adrenergic receptors antagonists)

Therapeutic Areas

Nervous System DiseasesOther DiseasesImmune System Diseases+ [2]

Active Indication-

Inactive Indication

Bipolar DisorderDepressive Disorder, MajorFibromyalgia+ [3]

Originator Organization

GSK Plc

Active Organization-

Inactive Organization

GSK Plc

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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Structure

Molecular FormulaC13H19Cl2NO2

InChIKeyORXTVTDGPVINDN-BTJVGWIPSA-N

CAS Registry106083-71-0

View All Structures (2)

Norepinephrine transporter (NET; encoded by SLC6A2) reuptakes the majority of the released noradrenaline back to the presynaptic terminals, thereby affecting the synaptic noradrenaline level¹. Genetic mutations and dysregulation of NET are associated with a spectrum of neurological conditions in humans, making NET an important therapeutic target¹. However, the structure and mechanism of NET remain unclear. Here we provide cryogenic electron microscopy structures of the human NET (hNET) in three functional states-the apo state, and in states bound to the substrate meta-iodobenzylguanidine (MIBG) or the orthosteric inhibitor radafaxine. These structures were captured in an inward-facing conformation, with a tightly sealed extracellular gate and an open intracellular gate. The substrate MIBG binds at the centre of hNET. Radafaxine also occupies the substrate-binding site and might block the structural transition of hNET for inhibition. These structures provide insights into the mechanism of substrate recognition and orthosteric inhibition of hNET.

19 Oct 2007·Postepy higieny i medycyny doswiadczalnej (Online)Q4 · MEDICINE

[Obesity: a review of currently used antiobesity drugs and new compounds in clinical development].

Q4 · MEDICINE

ReviewOA

Author: Zieba, Remigiusz

This review summarizes data on currently used antiobesity drugs and new compounds under clinical development. Three antiobesity drugs are currently accepted for long-term use. Sibutramine is a noradrenaline and serotonin reuptake inhibitor which reduces body weight by about 4-5 kg but increases heart rate and arterial blood pressure. Orlistat is a gastrointestinal lipase inhibitor which results in mean weight loss by about 3 kg and reduces the incidence of type 2 diabetes in patients with impaired glucose tolerance; however, adverse gastrointestinal effects have been observed. Rimonabant is an endocannabinoid CB1 receptor antagonist which induces a 4-5 kg mean weight loss and improves glycemic and lipid profiles, but it induces anxiety and depressive disorders. Unfortunately, there are no data on the chronic administration of these drugs. Other drugs can induce weight loss, e.g. some antidepressants, antiseizure agents, and antidiabetic drugs. The moderate efficacy of currently used antiobesity drugs has led to an intense effort to identify new, safe antiobesity drugs with better therapeutic profiles. The new antiobesity drugs under clinical development include: 1) agents that affect neurotransmitters in the central nervous system, including noradrenaline and dopamine reuptake inhibitors (bupropion, radafaxine), selective 5HT2C receptor agonists (lorcaserin), and selective 5HT6 receptor antagonists, 2) agents that modulate the activity of neuropeptides influencing food intake, including leptin analogues, human ciliary neurotrophic factor (Axokine), neuropeptide Y antagonists, and melanine-concentrating hormone antagonists, 3) agents that affect the peripheral satiety signals and brain-gut axis, e.g. selective cholecystokinin receptor A agonists, PYY3-36, agents decreasing ghrelin activity, 4) thermogenic agents, e.g. selective beta3 receptor agonists and selective thyroid hormone receptor beta agonists, and 5) others, e.g. human growth hormone fragment (AOD9604) and gastrointestinal lipase inhibitor (cetilistat).

01 Apr 2006·Current opinion in investigational drugs (London, England : 2000)

Obesity drugs in clinical development.

Review

Author: Halford, Jason C G

A number of anti-obesity drugs are currently undergoing clinical development. These include: (i) centrally-acting drugs, such as the noradrenergic and dopaminergic reuptake inhibitor radafaxine, the endocannabinoid antagonist rimonabant, the selective serotonin 5-HT2c agonist APD-356, and oleoyl-estrone; (ii) drugs that target peripheral episodic satiety signals, such as glucagon-like peptide-1 (exenatide, exenatide-LAR and liraglutide), peptide YY (intranasal PYY3-36 and AC-162325) and amylin (pramlintide); (iii) drugs that block fat absorption, such as the novel lipase inhibitors cetilistat and GT-389255; and (iv) a human growth hormone fragment (AOD-9604) that increases adipose tissue breakdown. Of these, only rimonabant has got as far as completing phase III clinical trials. This review will provide an overview of the most prominent drugs currently undergoing clinical development as potential anti-obesity therapies.

100 Deals associated with Radafaxine Hydrochloride

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External Link

KEGG	Wiki	ATC	Drug Bank
D05692	-	-	DB11790

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Depressive Disorder, Major	Phase 2	US	GSK Plc	01 Mar 2003
Bipolar Disorder	Phase 2	GB	GSK Plc	-
Fibromyalgia	Phase 2	GB	GSK Plc	-
Neuralgia	Phase 2	GB	GSK Plc	-
Obesity	Phase 2	GB	GSK Plc	-
Restless Legs Syndrome	Phase 2	GB	GSK Plc	-