Delving into the Latest Updates on GSK-598809 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

D3 receptor

Mechanism

D3 receptor antagonists(Dopamine D3 receptor antagonists)

Therapeutic Areas

Other DiseasesEndocrinology and Metabolic Disease

Active Indication-

Inactive Indication

AlcoholismFeeding and Eating DisordersNicotine Dependence+ [4]

Originator Organization

GSK Plc

Active Organization-

Inactive Organization

GSK Plc

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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Structure

Molecular FormulaC22H23F4N5OS

InChIKeyZKRWPAYTJMRKLJ-BTYIYWSLSA-N

CAS Registry863680-46-0

The purpose of this research study is to find out if an investigational drug, GSK598809 can help people who have very recently quit smoking; the investigators want to find out if continuing to take GSK598809 over six weeks can help prevent smokers from relapsing. To relapse means you "fall back" into smoking again after quitting. The investigators also want to find out if GSK598809 is safe to take without causing too many side effects.

Start Date01 Aug 2010

Sponsor / Collaborator

McLean Hospital, Inc.

[+2]

NCT00908206 / WithdrawnPhase 1

A Placebo-controlled, Single-blind, Cross-over, Randomised, fMRI Study Comparing Cue-induced Brain Activation Patterns After a Single Oral Dose of GSK598809 or Placebo in Abstinent Alcoholic Subjects

This study will compare the effects of GSK598809 and placebo in alcohol dependent volunteers. A placebo is a pill with no drug in it (i.e. dummy drug) but it is made to look exactly like the real drug.
Subjects will be given one dose of GSK598809 during one visit and placebo during the other visit. These dosing visits will be at least 1 week apart. The study is randomised, which means that a computer programme will decide by chance (like tossing a coin), the order in which subjects will receive GSK598809 or the placebo, or in other words, whether they will receive GSK598809 or placebo first.
The study is blinded, which means the subjects will not know whether they are receiving study drug or placebo first and neither will the doctors at the institute. If necessary for reasons of safety, the study staff can find out exactly what the subject has received.
The study will last for approximately 4 weeks but could be up to 6 weeks, depending on length of time between screening and dosing. From screening the subjects will be alcohol-abstinent, they may be put on medication for treatment of withdrawal symptoms and then will have at least 7 days without any medication before beginning the study medication. During the study the subjects will be inpatients at the Central Institute of Mental Health. All subjects will be required to fill out questionnaires, perform behavioural tasks and undergo MRI and functional MRI (fMRI) scans.

Start Date01 May 2009

Sponsor / Collaborator

GSK Plc

NCT01039454 / CompletedPhase 1

A Single-blind, Randomized, Placebo Controlled, Two-period Crossover fMRI Study to Investigate the Effects of the D3 Antagonist GSK598809 on Neural and Behavioural Responses to Food Reward and Reinforcement After a Single Oral Dose of GSK598809 in Overweight and Obese Subjects.

This novel compound is a new experimental treatment that may help people to stop compulsive overeating. Compulsive overeating or binge eating is one of the main reasons why people are overweight or obese. Recent research has shown that some kinds of overeating may be linked to a brain chemical called dopamine. There is some evidence that blocking the action of this chemical in animals can reduce food intake, particularly of foods that are high in fat and sugar. The purpose of this study is to find out if this compound (which blocks the effects of dopamine) has the same effect in overweight or obese people, as it does in animals.

Start Date18 Dec 2008

Sponsor / Collaborator

GSK Plc

100 Clinical Results associated with GSK-598809

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100 Translational Medicine associated with GSK-598809

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100 Patents (Medical) associated with GSK-598809

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16

Literatures (Medical) associated with GSK-598809

01 Dec 2019·Journal of Pharmacology and Experimental TherapeuticsQ3 · MEDICINE

Newly Developed Dopamine D₃Receptor Antagonists,R-VK4-40 andR-VK4-116, Do Not Potentiate Cardiovascular Effects of Cocaine or Oxycodone in Rats

Q3 · MEDICINE

Article

Author: Jordan, Chloe J ; Baumann, Michael H ; Xi, Zheng-Xiong ; Schindler, Charles W ; Shaik, Anver Basha ; Newman, Amy Hauck ; Thorndike, Eric B ; Humburg, Bree A

Opioid and cocaine abuse are major public health burdens. Existing medications for opioid use disorder are limited by abuse liability and side effects, whereas no treatments are currently approved in the United States for cocaine use disorder. Dopamine D₃ receptor (D₃R) antagonists have shown promise in attenuating opioid and cocaine reward and mitigating relapse in preclinical models. However, translation of D₃R antagonists to the clinic has been hampered by reports that the D₃R antagonists GSK598,809 (5-(5-((3-((1S,5R)-1-(2-fluoro-4-(trifluoromethyl)phenyl)-3-azabicyclo[3.1.0]hexan-3-yl)propyl)thio)-4-methyl-4H-1,2,4-triazol-3-yl)-4-methyloxazole) and SB-277,011A (2-(2-((1r,4r)-4-(2-oxo-2-(quinolin-4-yl)ethyl)cyclohexyl)ethyl)-1,2,3,4-tetrahydroisoquinoline-6-carbonitrile) have adverse cardiovascular effects in the presence of cocaine. Recently, we developed two structurally novel D₃R antagonists, R-VK4-40 and R-VK4-116, which are highly selective for D₃R and display translational potential for treatment of opioid use disorder. Here, we tested whether R-VK4-40 ((R)-N-(4-(4-(2-Chloro-3-ethylphenyl)piperazin-1-yl)-3-hydroxybutyl)-1H-indole-2-carboxamide) and R-VK4-116 ((R)-N-(4-(4-(3-Chloro-5-ethyl-2-methoxyphenyl)piperazin-1-yl)-3-hydroxybutyl)-1H-indole-2-carboxamide) have unwanted cardiovascular effects in the presence of oxycodone, a prescription opioid, or cocaine in freely moving rats fitted with surgically implanted telemetry transmitters. We also examined cardiovascular effects of the D₃R antagonist, SB-277,011A, and L-741,626 (1-((1H-indol-3-yl)methyl)-4-(4-chlorophenyl)piperidin-4-ol), a dopamine D₂ receptor-selective antagonist, for comparison. Consistent with prior reports, SB-277,011A increased blood pressure, heart rate, and locomotor activity alone and in the presence of cocaine. L-741,626 increased blood pressure and heart rate. In contrast, R-VK4-40 alone dose-dependently reduced blood pressure and heart rate and attenuated oxycodone-induced increases in blood pressure and oxycodone or cocaine-induced increases in heart rate. Similarly, R-VK4-116 alone dose-dependently reduced cocaine-induced increases in blood pressure and heart rate. These results highlight the safety of new D₃R antagonists and support the continued development of R-VK4-40 and R-VK4-116 for the treatment of opioid and cocaine use disorders. SIGNIFICANCE STATEMENT: Opioid and cocaine abuse are major public health challenges and new treatments that do not adversely impact the cardiovascular system are needed. Here, we show that two structurally novel dopamine D₃ receptor antagonists, R-VK4-40 and R-VK4-116, do not potentiate, and may even protect against, oxycodone- or cocaine-induced changes in blood pressure and heart rate, supporting their further development for the treatment of opioid and/or cocaine use disorders.

01 Aug 2017·Neuropsychopharmacology

Erratum: Acute D3 Antagonist GSK598809 Selectively Enhances Neural Response During Monetary Reward Anticipation in Drug and Alcohol Dependence

Author: Smith, Dana ; Paterson, Louise ; Suckling, John ; Ersche, Karen D. ; McGonigle, John ; Nutt, David J. ; Boyapati, Venkataramana ; Deakin, John F. W. ; Orban, Csaba ; Metastasio, Antonio ; Robbins, Trevor W. ; Kuchibatla, Shankar ; Taylor, Eleanor ; Passetti, Filippo ; Reed, Laurence ; Elliott, Rebecca ; Lingford-Hughes, Anne ; Nestor, Liam J. ; Murphy, Anna ; Flechais, Remy

This corrects the article DOI: 10.1038/npp.2016.289.

01 Jun 2017·NeuropsychopharmacologyQ1 · MEDICINE

Erratum: Acute D3 Antagonist GSK598809 Selectively Enhances Neural Response During Monetary Reward Anticipation in Drug and Alcohol Dependence

Q1 · MEDICINE

Article

Author: Smith, Dana ; Nestor, Liam J ; Paterson, Louise ; McGonigle, John ; Passetti, Filippo ; Taylor, Eleanor ; Orban, Csaba ; Lingford-Hughes, Anne ; Flechais, Remy ; Robbins, Trevor W ; Suckling, John ; Kuchibatla, Shankar ; Elliott, Rebecca ; Deakin, John FW ; Nutt, David J ; Metastasio, Antonio ; Boyapati, Venkataramana ; Murphy, Anna ; Reed, Laurence ; Ersche, Karen D

100 Deals associated with GSK-598809

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Nicotine Dependence	Phase 2	US	GSK Plc	01 Aug 2010
Alcoholism	Phase 2	-	GSK Plc	01 May 2009
Obesity	Phase 2	GB	GSK Plc	18 Dec 2008
Substance-Related Disorders	Phase 2	US	GSK Plc	01 Dec 2008
Unspecified drug dependence	Phase 2	GB	GSK Plc	01 Mar 2007
Unspecified drug dependence	Phase 2	GB	GSK Plc	01 Mar 2007
Feeding and Eating Disorders	Phase 2	GB	GSK Plc	-
Smoking Cessation	Phase 2	DE	GSK Plc	-
Smoking Cessation	Phase 2	US	GSK Plc	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01188967 (CTgov)	Phase 2	Nicotine Dependence	84	Placebo (Placebo Treatment Group)	dffronhkkj(idrredesjt) = cqfochfffz olwglbtusg (twdvhtsyde, zcyfseliep - flumqgelsh) View more	-	09 Jan 2017
				GSK598809 (GSK598809 Treatment Group)	dffronhkkj(idrredesjt) = pyjbtsmjti olwglbtusg (twdvhtsyde, kieivhzdmd - omrhdhfrxg) View more