Article
Clinical Neurology
Samantha N. Scott, Raul Garcia, Gregory L. Powell, Sophia M. Doyle, Brielle Ruscitti, Tien Le, Aracely Esquer, Kevin M. Blattner, Benjamin E. Blass, Janet L. Neisewander
Summary: The 5-HT1B receptor agonist CP94253 was found to decrease cocaine intake and seeking behavior in rats after resumption of cocaine self-administration, as well as reduce cue reactivity without affecting locomotion. These findings suggest that the inhibitory effects of CP94253 observed after abstinence are long-lasting and may have clinical efficacy as anti-relapse medications for cocaine use disorders.
JOURNAL OF PSYCHOPHARMACOLOGY
(2021)
Article
Neurosciences
Florence P. Varodayan, Reesha R. Patel, Alessandra Matzeu, Sarah A. Wolfe, Dallece E. Curley, Sophia Khom, Pauravi J. Gandhi, Larry Rodriguez, Michal Bajo, Shannon D'Ambrosio, Hui Sun, Tony M. Kerr, Rueben A. Gonzales, Lorenzo Leggio, Luis A. Natividad, Carolina L. Haass-Koffler, Remi Martin-Fardon, Marisa Roberto
Summary: This study sheds light on the crucial role of adrenergic receptors in the central amygdala (CeA) in alcohol use disorder (AUD) and uncovers the mechanisms underlying the association between specific adrenergic receptors and AUD. These findings are significant for the development of novel medications for the treatment of AUD.
BIOLOGICAL PSYCHIATRY
(2022)
Review
Neurosciences
Melinda Hersey, Amanda K. Bacon, Lydia G. Bailey, Mark A. Coggiano, Amy H. Newman, Lorenzo Leggio, Gianluigi Tanda
Summary: The rapid increase in individuals affected by psychostimulant use disorder (PSUD) has highlighted the potential of Modafinil (MOD) as a therapeutic option due to its non-addictive properties, despite its similar mechanism of action to commonly abused psychostimulants on the dopamine transporter (DAT). Clinical and preclinical studies have demonstrated the efficacy of MOD in treating symptoms related to PSUD and other psychiatric disorders involving alterations of brain dopamine systems.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Gastroenterology & Hepatology
Shin Fukudo, Masatoshi Nakamura, Tatsuto Hamatani, Kiyoyasu Kazumori, Hiroto Miwa
Summary: The study in Japan evaluated the efficacy and safety of minesapride in IBS-C patients, showing that minesapride increased stool frequency, reduced abdominal and overall IBS-C symptoms, and was well tolerated.
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
(2021)
Article
Clinical Neurology
Andrea Cippitelli, Gilles Zribi, Lawrence Toll
Summary: PPL-103 has shown potential as a pharmacotherapy for the treatment of cocaine use disorder (CUD). It reduces self-administration of cocaine, decreases motivation for cocaine, and attenuates binge-like cocaine taking. PPL-103 also reduces priming- and cue-induced reinstatement of cocaine seeking. Tolerance development was not observed with repeated PPL-103 treatment.
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
(2022)
Article
Cardiac & Cardiovascular Systems
Michael S. Valentine, Aaron M. Bender, Sheila Shay, Krista C. Paffenroth, Santhi Gladson, Jonathan W. Dickerson, Katherine J. Watson, Nicholas J. Kapolka, Olivier Boutaud, Jerri M. Rook, Timothy S. Blackwell, Bryan L. Roth, Fiona E. Harrison, Eric D. Austin, James D. West, Craig W. Lindsley, W. David Merryman
Summary: The aim of this study was to develop novel systemically restricted compounds targeting the 5-HT2B receptor. The novel 5-HT2B partial agonist, VU6047534, can both prevent and treat Sugen-hypoxia-induced pulmonary arterial hypertension. These findings provide new possibilities for the treatment of pulmonary arterial hypertension.
JACC-BASIC TO TRANSLATIONAL SCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Gisela Andrea Camacho-Hernandez, Andrea Casiraghi, Deborah Rudin, Dino Luethi, Therese C. Ku, Daryl A. Guthrie, Valentina Straniero, Ermanno Valoti, Gerhard J. Schutz, Harald H. Sitte, Amy Hauck Newman
Summary: The study used fluorescent ligands to investigate the function and distribution of monoamine transporters. By extending SAR for nisoxetine and talopram, high affinity rhodamine-labeled fluorescent probes were identified for the norepinephrine transporter (NET). Nisoxetine-based fluorescent probe 6 showed high binding affinity for NET and stained both NET and SERT in transporter-expressing cells at low concentrations.
RSC MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Tania Muller, Laurent Demizieux, Stephanie Troy-Fioramonti, Chloe Buch, Julia Leemput, Christine Belloir, Jean-Paul Pais De Barros, Tony Jourdan, Patricia Passilly-Degrace, Xavier Fioramonti, Anne-Marie Le Bon, Bruno Verges, Jean-Michel Robert, Pascal Degrace
Summary: JM-00266, a peripherally restricted CB1 receptor blocker, shows promising effects in improving metabolic disorders associated with obesity. It exhibits inverse agonist activity on CB1 receptors, counteracts anandamide-induced gastroparesis, and improves glucose tolerance and insulin sensitivity in wild-type mice.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Soichiro Ide, Toshitake Hirai, Takafumi Muto, Tomio Yamakawa, Kazutaka Ikeda
Summary: Opioid addiction and overdose are serious problems, and the development of new therapeutic options is crucial. This study evaluated a novel selective KOP agonist, NP-5497-KA, and found it to have high selectivity and fewer side effects compared to existing drugs, suggesting it may be a promising option for the treatment of opioid use disorder.
SCIENTIFIC REPORTS
(2023)
Article
Pharmacology & Pharmacy
Osama Refai, Shaili Aggarwal, Mary Hongying Cheng, Zayna Gichi, Joseph M. Salvino, Ivet Bahar, Randy D. Blakely, Ole Mortensen
Summary: In this study, we demonstrated that the allosteric modulator KM822 can decrease the affinity of cocaine and amphetamine for the dopamine transporter (DAT), suggesting a potential therapeutic application. Our findings also indicate that Caenorhabditis elegans can be used as a model to study allosteric modulation of DAT and its behavioral consequences, providing new insights into this field.
MOLECULAR PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Nasimudeen R. Jabir, Mohd Shahnawaz Khan, Nouf Omar Alafaleq, Huma Naz, Bakrudeen Ali Ahmed
Summary: This study evaluated the anticancer potential of yohimbine in drug-resistant oral cancer cells. The results showed that yohimbine increased cytotoxicity, induced apoptosis, generated ROS, and modulated MMP. The study suggests that yohimbine has potential as a repurposed drug, in addition to its aphrodisiac properties.
MOLECULAR BIOLOGY REPORTS
(2022)
Article
Neurosciences
Blazej D. Pedzich, Sarah Rubens, Mehdi Sekssaoui, Anouk Pierre, Andries Van Schuerbeek, Philippe Marin, Joel Bockaert, Emmanuel Valjent, Carine Becamel, Dimitri De Bundel
Summary: Psychedelic-assisted psychotherapy has gained attention as a novel treatment strategy for fear-related mental disorders. This study investigated the effect of activating the serotonin 2A (5-HT2A) receptor, a key target for psychedelics, on emotional processing. The findings suggest that activation of 5-HT2A receptors in the amygdala suppresses fear expression and reduces anxiety-like behavior, providing insights into the underlying mechanisms of psychedelic-assisted therapy.
NEUROPSYCHOPHARMACOLOGY
(2022)
Article
Clinical Neurology
Benjamin Berger, Ruediger Kornberger, Jasper Dingemanse
Summary: The study investigated the pharmacokinetic and pharmacodynamic interactions between daridorexant and citalopram in healthy subjects, showing no relevant effects on exposure levels between the two drugs. Co-administration with citalopram at steady state led to changes in pharmacodynamic assessments, while doses up to 50 mg of daridorexant were found to be safe when used concomitantly with citalopram.
EUROPEAN NEUROPSYCHOPHARMACOLOGY
(2021)
Article
Chemistry, Medicinal
Mu Yang, Peter G. Larson, Lincoln Brown, John R. Schultz, Tamara A. Kucaba, Thomas S. Griffith, David M. Ferguson
Summary: This study investigates the effect of isomeric substitutions to the C2-butyl group of imidazoquinoline agonists on Toll-like receptors (TLR) 7 and 8. The results show that the conformations of the dimeric receptor complex are highly sensitive to steric perturbations, indicating the importance of the ligand binding pocket in regulating the receptor signal. This finding has significant implications for the design of immunomodulatory agents.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Oncology
Maisoon Matareed, Eleftheria Maranou, Saara A. Koskela, Arfa Mehmood, Helen Kalirai, Sarah E. Coupland, Carlos R. Figueiredo
Summary: Loss of BAP1 gene expression in metastatic uveal melanoma triggers immunosuppressive mechanisms in the tumor microenvironment. PLIN2 expression serves as a prognostic biomarker in uveal melanoma. Loss of adipophilin expression is significantly associated with monosomy 3 status and nuclear BAP1 losses in uveal melanoma tumors.
JOURNAL OF PATHOLOGY
(2023)