Article
Pharmacology & Pharmacy
Estefania Moreno, Nil Casajuana-Martin, Michael Coyle, Baruc Campos Campos, Ewa Galaj, Claudia Llinas del Torrent, Arta Seyedian, William Rea, Ning-Sheng Cai, Alessandro Bonifazi, Benjamin Floran, Zheng-Xiong Xi, Xavier Guitart, Vicent Casado, Amy H. Newman, Christopher Bishop, Leonardo Pardo, Sergi Ferre
Summary: This study provides evidence that heteromerization of G protein-coupled receptors (GPCRs), specifically dopamine D1 and D3 receptors, can influence the pharmacological properties of selective ligands. In vivo experiments support the involvement of D1R-D3R heteromers in the development of L-DOPA-induced dyskinesia in Parkinson's disease, suggesting the potential of targeting GPCR heteromers for drug development.
PHARMACOLOGICAL RESEARCH
(2022)
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
Oncology
Pia Espanol, Ramon Rovira, Pablo Caruana, Rocio Luna-Guibourg, Cristina Soler, Natalia Teixeira, Francisco Rodriguez, Alberto Gallardo, Maria Edwards, Oriol Porta, Maria Gamez, Olga Sanchez, Elisa Llurba, Jose Luis Corchero, Maria Virtudes Cespedes
Summary: This study evaluated the expressions of ADRβ2, DRD1, and DRD2 in healthy tissues and endometrial tumors. It found that the expressions of DRD1 and DRD2 were closely associated with the clinic-pathological features of endometrial cancer, suggesting that the combined activation of DRD1 and blockade of DRD2 may be an innovative therapeutic strategy to inhibit tumor growth in EC.
GYNECOLOGIC ONCOLOGY
(2023)
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
Chemistry, Medicinal
Milica Elek, Mariam Dubiel, Laura Mayer, Aleksandra Zivkovic, Thomas J. J. Mueller, Holger Stark
Summary: This article describes the use of BOPPY fluorophores for labeling dopamine D2 and D3 receptor ligands, obtaining compounds with fluorescent properties. This method is widely applicable.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2022)
Review
Biochemistry & Molecular Biology
Kavya Prasad, Erik F. J. de Vries, Philip H. Elsinga, Rudi A. J. O. Dierckx, Aren van Waarde
Summary: Adenosine and dopamine interact antagonistically in living mammals via adenosine A(2A) and dopamine D-2 receptors. These interactions mainly occur in striatal neurons and astrocytes, and may have therapeutic potential for Parkinson's disease, schizophrenia, substance abuse, and attention deficit-hyperactivity disorder.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Thayssa Tavares da Silva Cunha, Rafaela Ribeiro Silva, Daniel Alencar Rodrigues, Pedro de Sena Murteira Pinheiro, Thales Kronenberger, Carlos Mauricio R. Sant'Anna, Francois Noel, Carlos Alberto Manssour Fraga
Summary: Most neurodegenerative diseases are multifactorial, and the molecular mechanisms related to their development are constantly advancing. Dopamine and dopaminergic receptor subtypes play a crucial role in the pathophysiology of various neurological disorders. Therefore, the dopaminergic system and dopamine receptor ligands are important for the treatment of these disorders.
Article
Biochemistry & Molecular Biology
Celine Legros, Anne Rojas, Clemence Dupre, Chantal Brasseur, Isabelle Riest-Fery, Olivier Muller, Jean-Claude Ortuno, Olivier Nosjean, Sophie-Penelope Guenin, Gilles Ferry, Jean A. Boutin
Summary: D3/D2 sub-specificity is a complex problem to solve due to the lack of easy structural biology of G-protein coupled receptors. This study used directed mutagenesis and basic binding experiments to explore a rational approach for the discovery of highly specific D3 ligands over D2 ligands. Stable expression of receptors in HEK cells was used to construct mutants and chimeras of D2 and D3 receptors, and their binding characteristics were analyzed using standard binding conditions. The study demonstrated the feasibility and potential of the approach.
Article
Clinical Neurology
Bing Chen, Jiangang Xu, Simiao Chen, Tingting Mou, Ying Wang, Haojun Wang, Zhihan Zhang, Feifan Ren, Zheng Wang, Kangyu Jin, Jing Lu
Summary: This study found that dysregulation of the dopamine system contributes to depressive-like behaviors in rats, and the neurological functions regulated by hypocretin are severely affected in depression. It also found that suvorexant plays a role in alleviating depression by affecting the dopamine system.
JOURNAL OF AFFECTIVE DISORDERS
(2023)
Review
Biochemistry & Molecular Biology
Kyeong-Man Kim
Summary: Dopamine receptors, specifically D2R and D3R, play important roles in regulating mood, motivation, reward, and movement. While D2R are widely distributed across the brain, D3R are primarily found in specific areas related to cognitive and emotional functions. Despite their similarities, D2R and D3R have distinct regulatory properties involving desensitization, endocytosis, posttranslational modification, and interactions with other cellular components.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Romain Gerbier, Delphine Ndiaye-Lobry, Pablo B. Martinez de Morentin, Erika Cecon, Lora K. Heisler, Philippe Delagrange, Florence Gbahou, Ralf Jockers
Summary: Functional fingerprint of heteromers composed of G(i)-coupled melatonin MT2 receptors and G(q)-coupled serotonin 5-HT2C receptors was identified in mouse brain, with melatonin activating G(q) proteins and PLC in a concentration-dependent manner in the hypothalamus and cerebellum. These effects were absent in cortex, inhibited by the 5-HT2C receptor-specific inverse agonist SB-243213, and were fully recapitulated in MT2 and 5-HT2C knockout mice. Furthermore, antidepressant agomelatine had similar effects to melatonin but blocked melatonin-promoted G(q) activation due to its 5-HT2C antagonistic component, providing strong functional evidence for the existence of MT2/5-HT2C heteromeric complexes.
Article
Pharmacology & Pharmacy
Zhongtang Li, Fan Fang, Yiyan Li, Xuehui Lv, Ruqiu Zheng, Peili Jiao, Yuxi Wang, Guiwang Zhu, Zefang Jin, Xiangqing Xu, Yinli Qiu, Guisen Zhang, Zhongjun Li, Zhenming Liu, Liangren Zhang
Summary: This study reports a class of derivatives with dopamine D3 receptor selectivity as potential antipsychotic drugs. One compound, named 36b, exhibits multiple antipsychotic-like properties, including inhibiting excessive activity in mice, reducing climbing behavior, and demonstrating antidepressant-like activity, without adverse effects on mouse body weight and prolactin levels.
ACTA PHARMACEUTICA SINICA B
(2023)
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
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.
Article
Radiology, Nuclear Medicine & Medical Imaging
Igor D. Grachev, Philipp M. Meyer, Georg A. Becker, Marcus Bronzel, Doug Marsteller, Gina Pastino, Ole Voges, Laura Rabinovich, Helena Knebel, Franziska Zientek, Michael Rullmann, Bernhard Sattler, Marianne Patt, Thilo Gerhards, Maria Strauss, Andreas Kluge, Peter Brust, Juha-Matti Savola, Mark F. Gordon, Michal Geva, Swen Hesse, Henryk Barthel, Michael R. Hayden, Osama Sabri
Summary: Pridopidine demonstrates high affinity for the S1R in clinical trials, with near complete occupancy at a clinically relevant single dose of 90 mg. Minimal occupancy is seen at the D2/D3R, indicating pridopidine's selectivity as an S1R ligand. The dose-S1R occupancy relationship suggests cooperative binding of pridopidine to the S1R.
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
(2021)
Article
Clinical Neurology
Marta Capannolo, Irene Fasciani, Stefania Romeo, Gabriella Aloisi, Mario Rossi, Pierangelo Bellio, Giuseppe Celenza, Benedetta Cinque, Maria Grazia Cifone, Marco Scarselli, Roberto Maggio
EUROPEAN NEUROPSYCHOPHARMACOLOGY
(2015)
Article
Clinical Neurology
Roberto Maggio, Marco Scarselli, Marta Capannolo, Mark J. Milian
EUROPEAN NEUROPSYCHOPHARMACOLOGY
(2015)
Article
Clinical Neurology
Marta Capannolo, Carmela Ciccarelli, Raffaella Molteni, Fabio Fumagalli, Cristina Rocchi, Stefania Romeo, Irene Fasciani, Gabriella Aloisi, Bianca M. Zani, Marco A. Riva, Roberto Maggio
Article
Multidisciplinary Sciences
Stefania Romeo, Daniela Di Camillo, Alessandra Splendiani, Marta Capannolo, Cristina Rocchi, Gabriella Aloisi, Irene Fasciani, Giovanni U. Corsini, Eugenio Scarnati, Luca Lozzi, Roberto Maggio
SCIENTIFIC WORLD JOURNAL
(2014)
Article
Humanities, Multidisciplinary
Franco Giorgi, Luis Emilio Bruni, Roberto Maggio
Review
Chemistry, Medicinal
Marco Carli, Shivakumar Kolachalam, Biancamaria Longoni, Anna Pintaudi, Marco Baldini, Stefano Aringhieri, Irene Fasciani, Paolo Annibale, Roberto Maggio, Marco Scarselli
Summary: Atypical antipsychotics can cause metabolic syndrome, including weight gain, dyslipidemia, type 2 diabetes, and high blood pressure. Olanzapine and clozapine have the highest risk of metabolic alterations, while newer medications like ziprasidone and lurasidone may be more tolerable in terms of metabolic profile. Differences in efficacy among antipsychotics should be considered, with clozapine being the most effective but potentially associated with increased metabolic risks. A multidisciplinary approach combining psychoeducation and therapeutic drug monitoring is proposed as a first-line strategy to avoid metabolic syndrome.
Article
Biochemistry & Molecular Biology
Matteo Cassandri, Silvia Pomella, Alessandra Rossetti, Francesco Petragnano, Luisa Milazzo, Francesca Vulcano, Simona Camero, Silvia Codenotti, Francesca Cicchetti, Roberto Maggio, Claudio Festuccia, Giovanni Luca Gravina, Alessandro Fanzani, Francesca Megiorni, Marialuigia Catanoso, Cinzia Marchese, Vincenzo Tombolini, Franco Locatelli, Rossella Rota, Francesco Marampon
Summary: The study evaluated the effects of MS-275 in combination with radiation therapy on RMS cells, showing that MS-275 could enhance radio-sensitivity and affect cell growth and DNA repair mechanisms through multiple pathways.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Roberto Maggio, Irene Fasciani, Marco Carli, Francesco Petragnano, Francesco Marampon, Mario Rossi, Marco Scarselli
Summary: The passage discusses the importance of information exchange and interpretation in biology, particularly in how cells integrate signals from various molecules. G protein-coupled receptors (GPCRs) play a crucial role in signal recognition and transduction within cells, and their formation of higher order oligomers helps organize cell compartments along the membrane. This structural basis allows for cells to perceive and discriminate localized increases in second messengers, contributing to the understanding of physiological roles played by receptor homo- and hetero-oligomerization in cell biology.
Article
Chemistry, Medicinal
Marco Carli, Eleonora Risaliti, Mena Francomano, Shivakumar Kolachalam, Biancamaria Longoni, Guido Bocci, Roberto Maggio, Marco Scarselli
Summary: This study reports the drug plasma concentrations of lithium and valproic acid in bipolar patients undergoing treatment at an Italian clinical center. Both lithium and valproic acid are commonly used drugs for bipolar disorder, and therapeutic drug monitoring is strongly recommended. The study found that a significant number of patients had subtherapeutic drug concentrations during their treatment, indicating the need for improvement in pharmacological treatments.
Review
Biochemistry & Molecular Biology
Irene Fasciani, Marco Carli, Francesco Petragnano, Francesco Colaianni, Gabriella Aloisi, Roberto Maggio, Marco Scarselli, Mario Rossi
Summary: The architecture of eukaryotic cells is defined by extensive membrane-delimited compartments, which allows G protein-coupled receptors (GPCRs) to signal from intracellular compartments and regulate different cell pathways. This review summarizes the current knowledge of GPCR signaling compartmentalization, including how GPCRs reach intracellular sites, are stimulated by ligands, and their potential physiological/pathophysiological roles. The modulation of compartmentalized GPCR signaling by drugs and ligands is also discussed.
Article
Oncology
Silvia Sideri, Francesco Petragnano, Roberto Maggio, Simonetta Petrungaro, Angela Catizone, Luisa Gesualdi, Viviana De Martino, Giulia Battafarano, Andrea Del Fattore, Domenico Liguoro, Paola De Cesaris, Antonio Filippini, Francesco Marampon, Anna Riccioli
Summary: The study found that highly metastatic prostate cancer cells show increased sensitivity to Docetaxel after radiotherapy failure and suggests immediate chemotherapy after radiotherapy failure may benefit certain patients. Furthermore, using a higher dose per fraction for radiotherapy in castration-resistant prostate cancer cells was not successful, but the results may vary between different cell lines.
Review
Biochemistry & Molecular Biology
Serena Barachini, Letizia Biso, Shivakumar Kolachalam, Lacopo Petrini, Roberto Maggio, Marco Scarselli, Biancamaria Longoni
Summary: Pancreatic islet transplantation is a treatment for Type 1 diabetic patients, and mesenchymal stem cells (MSCs) have shown potential in controlling graft rejection. MSCs can interact with immune system cells through direct contact or their secretome. This review discusses the role of MSCs in controlling the immune system and promoting repair in pancreatic islet transplantation, as well as challenges such as oxidative stress and impaired vasculogenesis. Preconditioning MSCs with hypoxia exposure or using stem cells with angiogenic potential in organoids may help improve transplant outcomes.
Review
Biochemistry & Molecular Biology
Roberto Maggio, Irene Fasciani, Francesco Petragnano, Maria Francesca Coppolino, Marco Scarselli, Mario Rossi
Summary: Unstructured regions in functional proteins, specifically the i3 loop and C-terminus in G protein-coupled receptors (GPCRs), have been recognized as crucial elements in GPCR function and regulation. They play critical roles in allosterically regulating GPCR activation, as autoregulators in receptor coupling specificity, and in facilitating receptor stability and interactions with intracellular protein partners.
Review
Chemistry, Medicinal
Irene Fasciani, Francesco Petragnano, Gabriella Aloisi, Francesco Marampon, Marco Carli, Marco Scarselli, Roberto Maggio, Mario Rossi
Article
Psychiatry
Monica Piersanti, Marta Capannolo, Maurizio Turchetti, Nicola Serroni, Domenico De Berardis, Pina Evangelista, Paola Costantini, Antonio Orsini, Alessandro Rossi, Roberto Maggio
RIVISTA DI PSICHIATRIA
(2014)
