ArticleThe Journal of pharmacology and experimental therapeutics2015
Dopamine D3 Receptor Antagonist (GSK598809) Potentiates the Hypertensive Effects of Cocaine in Conscious, Freely-Moving Dogs.
Article in The Journal of pharmacology and experimental therapeutics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.
- ACVIM consensus statement: Guidelines for the identification, evaluation, and management of systemic hypertension in dogs and cats.Journal of veterinary internal medicine · 2018Guideline
- Developing the Dopamine D3 Receptor (D3R) Antagonist, (R)-VK4-116, as a Non-Opioid Medication for the Treatment of Opioid Use Disorder.Medicinal research reviews · 2026Review
- Discovery, Characterization, and Optimization of a Novel Positive Allosteric Modulator-Antagonist of the DJournal of medicinal chemistry · 2025Article
- 2-Phenylcyclopropylmethylamine (PCPMA) Derivatives as DInternational journal of molecular sciences · 2025Article
- Study of Cytotoxicity of 3-Azabicyclo[3.1.0]hexanes and Cyclopropa[International journal of molecular sciences · 2025Article
- Study of Cytotoxicity of Spiro-Fused [3-Azabicyclo[3.1.0]hexane]oxindoles and Cyclopropa[a]pyrrolizidine-oxindoles Against Tumor Cell Lines.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Substance Addiction Rehabilitation Drugs.Pharmaceuticals (Basel, Switzerland) · 2024Review
- In vitro safety evaluation of dopamine D3R antagonist, R-VK4-116, as a potential medication for the treatment of opioid use disorder.PloS one · 2024Article
- Effects of selective dopamine D3 receptor partial agonist/antagonists on oxycodone self-administration and antinociception in monkeys.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Article
- Carbazole and tetrahydro-carboline derivatives as dopamine DActa pharmaceutica Sinica. B · 2023Article
- The D3 receptor antagonist SR 21502 reduces cue-induced reinstatement of methamphetamine-seeking in rats.Neuroscience letters · 2023Article
- Dopamine Receptor DThe Yale journal of biology and medicine · 2023Review
- Design and Synthesis of Conformationally Flexible Scaffold as Bitopic Ligands for Potent DInternational journal of molecular sciences · 2022Article
- A highly DNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2022Article
- Biological Evaluation of 3-Azaspiro[Bicyclo[3.1.0]Hexane-2,5'-Pyrimidines] as Potential Antitumor Agents.International journal of molecular sciences · 2022Article
- Low-dose polypharmacology targeting dopamine D1 and D3 receptors reduces cue-induced relapse to heroin seeking in rats.Addiction biology · 2021Article
- Novel Dual-Target μ-Opioid Receptor and Dopamine DJournal of medicinal chemistry · 2021Article
- New Drugs, Old Targets: Tweaking the Dopamine System to Treat Psychostimulant Use Disorders.Annual review of pharmacology and toxicology · 2021Article
- (±)VK4-40, a novel dopamine DBritish journal of pharmacology · 2020Article
- (-)-Stepholidine blocks expression, but not development, of cocaine conditioned place preference in rats.Neuroscience letters · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The chronic and relapsing nature of addiction presents unique challenges for ensuring the safety of a potential medication. A patient may use cocaine, for example, while taking the medication or take more medication than prescribed. Thus, a potential medication must be safe and not exacerbate the effects of cocaine. Multiple published studies support antagonism of brain dopamine D3 receptor function as a potential mechanism of action for an anti-addiction medication. Dopamine D3 receptors are widely distributed outside the central nervous system, however; for example, dopamine D3 receptors in the kidneys are implicated in regulating blood pressure. The selective dopamine D3 receptor antagonist GSK598809 [1-(2-fluoro-4-trifluoromethyl-phenyl)-3-{3-[4-methyl-5-(4-methyl-oxazol-5-yl)-4H-[1,2,4]triazol-3-ylsulfanyl]-propyl}-3-aza-bicyclo[3.1.0]hexane] has been proposed as a medication to treat cocaine and other substance use disorders. The US Food and Drug Administration has established guidelines recommending safety studies to investigate potential undesirable pharmacodynamic effects of a substance in relation to exposure in the therapeutic range and above. Hence, we assessed the interaction between this selective dopamine D3 receptor antagonist and cocaine on hemodynamics and cardiac function in freely-moving, telemetered dogs before conducting a clinical trial. GSK598809 increased the hemodynamic effect of cocaine in this model. Thus, the increase in blood pressure after intravenous cocaine was greater in animals that had been pretreated with GSK598809 compared with vehicle. This finding suggests that GSK598809 in particular, and perhaps dopamine D3 receptor antagonists as a class, may produce unacceptable cardiovascular risks as medications to treat cocaine use disorder.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.