Article
Psychiatry
Ioanna A. Vamvakopoulou, Leon Fonville, Alexandra Hayes, John McGonigle, Rebecca Elliott, Karen D. Ersche, Remy Flechais, Csaba Orban, Anna Murphy, Dana G. Smith, John Suckling, Eleanor M. Taylor, Bill Deakin, Trevor W. Robbins, David J. Nutt, Anne R. Lingford-Hughes, Louise M. Paterson
Summary: This study investigated the effects of a selective D3 receptor antagonist on the neural response to negative emotional processing in substance dependent individuals and healthy controls. The results showed that the D3 antagonist could modulate the BOLD response to aversive image processing, providing evidence for its potential therapeutic role in emotional regulation.
FRONTIERS IN PSYCHIATRY
(2022)
Article
Chemistry, Medicinal
Jin Cai, Mingqi Huang, Yuhong Wang, Xixi Chen, Min Ji
Summary: Three series of novel bitopic benzopyranomorpholine analogues were designed, synthesized, and evaluated for their selective ligand activity for the dopamine D3 receptor. Most compounds showed strong binding affinities and selectivity for the D3 receptor. One compound, 20h, demonstrated nanomolar affinity for the D3 receptor and exhibited anti-drug addiction efficacy in animal models.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Biochemistry & Molecular Biology
Peiyu Xu, Sijie Huang, Chunyou Mao, Brian E. Krumm, X. Edward Zhou, Yangxia Tan, Xi-Ping Huang, Yongfeng Liu, Dan-Dan Shen, Yi Jiang, Xuekui Yu, Hualiang Jiang, Karsten Melcher, Bryan L. Roth, Xi Cheng, Yan Zhang, H. Eric Xu
Summary: The study reported two cryo-EM structures of human D3R in complex with an inhibitory G protein and bound to D3R-selective agonists PD128907 and pramipexole, revealing distinct agonist binding modes and conformational signatures for ligand-induced receptor activation, providing insights for designing specific ligands to treat CNS diseases targeting the dopaminergic system.
Review
Psychiatry
M. Carmen Blanco-Gandia, Sandra Montagud-Romero, Marta Rodriguez-Arias
Summary: Various factors influence an individual's vulnerability to drug addiction, including hedonic eating activating reward circuits and the global increase in obesity rates affecting children and young people. The comorbidity between eating disorders and drug addiction has been a focus of recent research. Integrated responses are needed for patients with substance use and binge eating disorders.
WORLD JOURNAL OF PSYCHIATRY
(2021)
Review
Biochemistry & Molecular Biology
Kathryn Lanza, Christopher Bishop
Summary: Parkinson's Disease (PD) and long-term L-DOPA treatment induce plasticity that contributes to L-DOPA-induced dyskinesia (LID), with the dopamine D3 receptor (D3R) emerging as a promising target in LID management due to its upregulation in LID. D3R undergoes dynamic changes in both PD and LID, and recent genetic and pharmacologic tools have helped clarify its role in LID.
Article
Biochemistry & Molecular Biology
Hongshan Jin, Chengjun Wu, Rui Su, Tiemin Sun, Xingzhou Li, Chun Guo
Summary: The importance of identifying new D3R ligands was highlighted. Through virtual screening and binding assays, 37 potential compounds were identified. By using molecular dynamics simulation and binding free-energy calculations, more accurate and reliable D3R-ligand binding poses were obtained.
Article
Chemistry, Medicinal
Gui-Long Tian, Chia-Ju Hsieh, Michelle Taylor, Aladdin A. Riad, Robert R. Luedtke, Robert H. Mach
Summary: The difference in the secondary binding site between D2R and D3R has been utilized to design compounds with selectivity for D3R. This study prepared a series of bitopic ligands based on Fallypride to improve the selectivity for D3R using various secondary binding fragments. The results showed that compounds with a small alkyl group containing a heteroatom exhibited improved D3R selectivity.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Medicine, Research & Experimental
Xiaoyan Ding, Mengdie Yang, Ning Wu, Jin Li, Rui Song
Summary: Abnormal fear memory can lead to stress disorders such as PTSD. Therefore, intervention in the formation of abnormal fear memory can be a new strategy for preventing and treating PTSD.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
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
Biochemistry & Molecular Biology
Pramisha Adhikari, Bing Xie, Ana Semeano, Alessandro Bonifazi, Francisco O. Battiti, Amy H. Newman, Hideaki Yano, Lei Shi
Summary: The study focuses on developing D3R selective agonists over D2R and identifies compound AB04-88 with significant D3R selectivity and G protein bias. The chirality of the primary pharmacophore is key in conferring improved D3R potency, selectivity, and G protein signaling bias.
Article
Biochemistry & Molecular Biology
Boeun Lee, Michelle Taylor, Suzy A. Griffin, Tamara McInnis, Nathalie Sumien, Robert H. Mach, Robert R. Luedtke
Summary: The study showed that N-phenylpiperazine analogs can selectively bind to the human D3 dopamine receptor with significant D3 vs. D2 binding selectivity, potentially leading to the development of pharmacotherapeutics for levodopa-induced dyskinesia in patients with Parkinson's disease.
Article
Pharmacology & Pharmacy
Cristina Cosi, Jean-Claude Martel, Agnes L. Auclair, Ginetta Collo, Laura Cavalleri, Peter Heusler, Ludovic Leriche, Florence Gaudoux, Pierre Sokoloff, Paul C. Moser, Silvia Gatti-McArthur
Summary: F17464 is a new potential antipsychotic with a unique profile, showing high affinity for dopamine receptor subtype 3 and serotonin receptor subtype 1a, while having lower affinity for dopamine receptor subtype 2. It has demonstrated various neurochemistry and behavioral effects, suggesting therapeutic potential for schizophrenia and autism.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Cell Biology
Alicia Rivera, Diana Suarez-Boomgaard, Cristina Miguelez, Alejandra Valderrama-Carvajal, Jerome Baufreton, Kirill Shumilov, Anne Taupignon, Belen Gago, M. Angeles Real
Summary: Long-term exposure to morphine induces structural and synaptic plasticity in reward-related regions of the brain, playing a critical role in addiction. However, the morphine-induced neuroadaptations in the dorsal striatum, which is crucial for drug-related habit learning, have not been well studied. This study finds that prolonged treatment with morphine leads to retraction of dendritic arbor and loss of dendritic spines in the dorsal striatal projection neurons. Additionally, the dopamine D-4 receptor (D4R) is found to modulate striatal morphine-induced plasticity, as the combined treatment of morphine with a D4R agonist restores dendritic arbor and spine density while altering the electrical properties of the neurons.
Article
Neurosciences
Shi-Zhuang Wei, Xiao-Yu Yao, Chen-Tao Wang, An-Qi Dong, Dan Li, Yu-Ting Zhang, Chao Ren, Jin-Bao Zhang, Cheng-Jie Mao, Fen Wang, Chun-Feng Liu
Summary: Depression is a strong predictor of quality of life in PD patients, but there is lack of clear guidance on its treatment. Pramipexole, a dopamine agonist, has shown clinically useful effects in treating depression in PD along with improvements in bradykinesia. The antidepressive effect of pramipexole is mediated by DRD3 but not DRD2, suggesting the need for novel dopamine agonists specifically targeting DRD3 for future depression treatment in PD.
BRAIN RESEARCH BULLETIN
(2021)
Article
Chemistry, Medicinal
Benjamin E. Blass, Peng-Jen Chen, Michelle Taylor, Suzy A. Griffin, John C. Gordon, Robert R. Luedtke
Summary: Dopamine is a neurotransmitter linked to various diseases. This study reports a series of novel D-3 ligands with improved solubility compared to previous compounds.
MEDICINAL CHEMISTRY RESEARCH
(2022)
Article
Chemistry, Medicinal
Fabio Del Bello, Alessandro Bonifazi, Mario Giannella, Gianfabio Giorgioni, Alessandro Piergentili, Riccardo Petrelli, Carlo Cifani, Maria Vittoria Micioni Di Bonaventura, Thomas M. Keck, Angelica Mazzolari, Giulio Vistoli, Antonio Cilia, Elena Poggesi, Rosanna Matucci, Wilma Quaglia
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2017)
Article
Chemistry, Medicinal
Mayako Michino, Comfort A. Boateng, Prashant Donthamsetti, Hideaki Yano, Oluyomi M. Bakare, Alessandro Bonifazi, Michael P. Ellenberger, Thomas M. Keck, Vivek Kumar, Clare Zhu, Ravi Verma, Jeffrey R. Deschamps, Jonathan A. Javitch, Amy Hauck Newman, Lei Shi
JOURNAL OF MEDICINAL CHEMISTRY
(2017)
Article
Biochemistry & Molecular Biology
Fabio Del Bello, Dario Ambrosini, Alessandro Bonifazi, Amy H. Newman, Thomas M. Keck, Mario Giannella, Gianfabio Giorgioni, Alessandro Piergentili, Loredana Cappellacci, Antonio Cilia, Silvia Franchini, Wilma Quaglia
ACS CHEMICAL NEUROSCIENCE
(2019)
Article
Chemistry, Medicinal
Thomas M. Keck, R. Benjamin Free, Marilyn M. Day, Sonvia L. Brown, Michele S. Maddaluna, Griffin Fountain, Charles Cooper, Brooke Fallon, Matthew Holmes, Christopher T. Stang, Russell Burkhardt, Alessandro Bonifazi, Michael P. Ellenberger, Amy H. Newman, David R. Sibley, Chun Wu, Comfort A. Boateng
JOURNAL OF MEDICINAL CHEMISTRY
(2019)
Article
Behavioral Sciences
Alexander Batterman, James DeChiara, Ariful Islam, Megan B. Brenner, Bradford D. Fischer, Russell J. Buono, Thomas M. Keck, Thomas N. Ferraro
EPILEPSY & BEHAVIOR
(2019)
Article
Chemistry, Medicinal
Amy E. Moritz, R. Benjamin Free, Warren S. Weiner, Emmanuel O. Akano, Disha Gandhi, Ara Abramyan, Thomas M. Keck, Marc Ferrer, Xin Hu, Noel Southall, Joseph Steiner, Jeffrey Aube, Lei Shi, Kevin J. Frankowski, David R. Sibley
JOURNAL OF MEDICINAL CHEMISTRY
(2020)
Article
Neurosciences
Catherine A. Schweppe, Caitlin Burzynski, Subramaniam Jayanthi, Bruce Ladenheim, Jean Lud Cadet, Eliot L. Gardner, Zheng-Xiong Xi, Henriette van Praag, Amy Hauck Newman, Thomas M. Keck
PSYCHOPHARMACOLOGY
(2020)
Article
Neurosciences
Mohammad A. Rahman, Thomas M. Keck, Michael M. Poe, Dishary Sharmin, James M. Cook, Bradford D. Fischer
Summary: The combination of methyl 8-ethynyl-6-(pyridin-2-yl)-4H-benzo[f]imidazo[1,5-a][1,4]diazepine-3-carboxylate (MP-III-024) and morphine showed synergistic effects in preclinical models of mechanical hyperalgesia and thermal nociception, suggesting potential for combination therapy in pain-related disorders.
PSYCHOPHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Alessandro Bonifazi, Amy H. Newman, Thomas M. Keck, Silvia Gervasoni, Giulio Vistoli, Fabio Del Bello, Gianfabio Giorgioni, Pegi Pavletic, Wilma Quaglia, Alessandro Piergentili
Summary: The study identifies novel compounds targeting D3R or multiple targets, potentially useful for central nervous system disorders. Specific derivatives, such as 6,6-diphenyl-1,4-dioxane derivative 3 and 5,5-diphenyl-1,4-dioxane and 1,4-benzodioxane derivatives 6 and 9, display promising profiles for novel antipsychotic agents.
ACS CHEMICAL NEUROSCIENCE
(2021)
Meeting Abstract
Biochemistry & Molecular Biology
Thomas M. Keck, Shreya Kelshikar, Nisha Shah, Connor McBride, Moises Ximello Sanchez, Diandra Panasis, Brianna Maslonka, Abigail Muccilli, Maria Ladik, Ebrar Akca, Sophia Ginet
Meeting Abstract
Biochemistry & Molecular Biology
Sara Uribe, Eric J. DiDomenico, Christa M. Donegan, Yulista Tapia, Jason Conviser, Rohit R. Nambiar, Amy A. Juarez, Christine M. Side, Danya Aldaghma
Review
Biochemical Research Methods
Atlas M. Sardoo, Shaoqiang Zhang, Thomas N. Ferraro, Thomas M. Keck, Yong Chen
Summary: Understanding how memories are formed and stored in the brain is a fundamental question in neuroscience and computational biology. Recent advancements in single-cell RNA sequencing and single-nucleus RNA sequencing offer promising approaches to study memory-specific genes, their regulatory networks, and combinatorial patterns. This article reviews the experimental and computational procedures of these techniques and discusses their applications in human brain diseases and mouse models, as well as the computational challenges in understanding the regulatory mechanisms underlying long-term memory formation.
BRIEFINGS IN BIOINFORMATICS
(2022)
Review
Endocrinology & Metabolism
Sergi Ferre, Annabelle M. Belcher, Jordi Bonaventura, Cesar Quiroz, Marta Sanchez-Soto, Veronica Casado-Anguera, Ning-Sheng Cai, Estefania Moreno, Comfort A. Boateng, Thomas M. Keck, Benjamin Floran, Christopher J. Earley, Francisco Ciruela, Vicent Casado, Marcelo Rubinstein, Nora D. Volkow
Summary: The dopamine D4 receptor and its polymorphic variants play important roles in dopaminergic and noradrenergic modulation, and are associated with various disorders such as impulse-control disorders. Research on the D4 receptor helps to understand the regulatory mechanisms of impulsivity as a personality trait, and provides valuable therapeutic targets for diseases such as ADHD.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Chemistry, Medicinal
Ariful Islam, Mohammad Atiqur Rahman, Megan B. Brenner, Allamar Moore, Alyssa Kellmyer, Harley M. Buechler, Frank DiGiorgio, Vincent R. Verchio, Laura McCracken, Mousumi Sumi, Robert Hartley, Joseph R. Lizza, Gustavo Moura-Letts, Bradford D. Fischer, Thomas M. Keck
ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE
(2020)
Meeting Abstract
Biochemistry & Molecular Biology
Marilyn M. Day, R. Benjamin Free, Christopher R. T. Stang, Comfort A. Boateng, Thomas M. Keck, David R. Sibley