ArticlePsychopharmacology2010
Effectiveness of analogs of the kappa opioid receptor antagonist (3R)-7-hydroxy-N-((1S)-1-{[(3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethyl-1-piperidinyl]methyl}-2-methylpropyl)-1,2,3,4-tetrahydro-3-isoquinolinecarboxamide (JDTic) to reduce U50,488-induced diuresis and stress-induced cocaine reinstatement in rats.
Article in Psychopharmacology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
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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.
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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.
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Who cites it
31 citing papers in PubMed, 40 citations in OpenAlex.
- Cocaine use reduction with buprenorphine (CURB): rationale, design, and methodology.Contemporary clinical trials · 2013Trial
- Kappa opioid receptor antagonism in neuropsychiatry: from molecular mechanisms to clinical prospects.European archives of psychiatry and clinical neuroscience · 2026Review
- KOR agonists for the treatment and/or prevention of opioid use disorder and cocaine use disorder.Pharmacology, biochemistry, and behavior · 2025Review
- Kappa Opioid Agonist-Induced Diuresis: Characteristics, Mechanisms, and Beyond.Handbook of experimental pharmacology · 2022Article
- Consideration of sex as a biological variable in the translation of pharmacotherapy for stress-associated drug seeking.Neurobiology of stress · 2021Review
- Effects of Kappa opioid receptor blockade by LY2444296 HCl, a selective short-acting antagonist, during chronic extended access cocaine self-administration and re-exposure in rat.Psychopharmacology · 2020Article
- Effect of chronic alcohol vapor exposure on reinstatement of alcohol seeking induced by U50,488.Neuropharmacology · 2019Article
- Anti-stress neuropharmacological mechanisms and targets for addiction treatment: A translational framework.Neurobiology of stress · 2018Review
- Preclinical evaluation of the kappa-opioid receptor antagonist CERC-501 as a candidate therapeutic for alcohol use disorders.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2018Article
- Role of κ-Opioid Receptors in the Bed Nucleus of Stria Terminalis in Reinstatement of Alcohol Seeking.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2018Article
- Pharmacodynamic Relationships between Duration of Action of JDTic-like Kappa-Opioid Receptor Antagonists and Their Brain and Plasma Pharmacokinetics in Rats.ACS chemical neuroscience · 2016Article
- Ester Hydrolysis Differentially Reduces Aconitine-Induced Anti-hypersensitivity and Acute Neurotoxicity: Involvement of Spinal Microglial Dynorphin Expression and Implications forFrontiers in pharmacology · 2016Article
- Stress-Induced Reinstatement of Drug Seeking: 20 Years of Progress.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2016Review
- The non-peptide GLP-1 receptor agonist WB4-24 blocks inflammatory nociception by stimulating β-endorphin release from spinal microglia.British journal of pharmacology · 2015Article
- Design, synthesis, and biological evaluation of (3R)-1,2,3,4-tetrahydro-7-hydroxy-N-[(1S)-1-[[(3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethyl-1-piperidinyl]methyl]-2-methylpropyl]-3-isoquinolinecarboxamide (JDTic) analogues: in vitro pharmacology and ADME profile.Journal of medicinal chemistry · 2014Article
- The discovery and development of the N-substituted trans-3,4-dimethyl-4-(3'-hydroxyphenyl)piperidine class of pure opioid receptor antagonists.ChemMedChem · 2014Review
- The role of kappa opioid receptors in stress-induced reinstatement of alcohol seeking in rats.Brain and behavior · 2014Article
- Stress and VTA synapses: implications for addiction and depression.The European journal of neuroscience · 2014Review
- Characterization of BU09059: a novel potent selective κ-receptor antagonist.ACS chemical neuroscience · 2014Article
- Role of kappa-opioid receptors in stress and anxiety-related behavior.Psychopharmacology · 2013Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
rationaleThe kappa opioid receptor (KOR) antagonist, JDTic, was reported to prevent stress-induced reinstatement of cocaine-maintained responding and to have antidepressant-like effects.
objectivesOur objectives were to determine whether analogs of JDTic retained KOR antagonist activity and whether an orally effective analog prevented footshock-induced cocaine reinstatement.
methodsRTI-194 (i.g. 1-30 mg/kg, s.c. 0.3-10 mg/kg, and i.p. 30 mg/kg), RTI-212 (s.c. 0.3-10 mg/kg and i.p. 30 mg/kg), and RTI-230 (i.g. 3-30 mg/kg and i.p. 1-30 mg/kg) were evaluated for their ability to block diuresis induced by 10-mg/kg U50,488 in rats. RTI-194 was additionally evaluated i.g. (3-100 mg/kg) for its ability to prevent footshock-induced reinstatement of responding previously reinforced with 0.5-mg/kg/inf cocaine.
resultsRTI-194 significantly (p < 0.05) attenuated U50,488-induced diuresis when given i.g., s.c., and i.p. RTI-194s effectiveness increased 1 week following administration. RTI-212 was ineffective. RTI-230 was ineffective when given i.g., but blocked diuresis at 24 h and 8 days (1, 10, and 30 mg/kg), 15 days (10 and 30 mg/kg), 22 and 29 days (30 mg/kg) following i.p. administration. Footshock reinstated responding in vehicle-but not RTI-194 (30 and 100 mg/kg)-treated rats.
conclusionsRTI-194 and RTI-230 are effective KOR antagonists, and RTI-194 is now included with JDTic as the only reported compounds capable of antagonizing the KOR following oral administration. The failure of stress to reinstate cocaine seeking in rats treated with RTI-194 is consistent with results reported with JDTic, although it had less efficacy in lowering response levels than JDTic, suggesting a diminished overall effectiveness relative to it.
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