Review
Behavioral Sciences
Daisuke Ibi
Summary: The serotonergic and glutamatergic neurotransmitter systems play a crucial role in the pathophysiology of schizophrenia and interact functionally. Understanding the crosstalk between these systems is important for regulating brain function and behavioral symptoms in schizophrenia patients.
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
(2022)
Article
Chemistry, Multidisciplinary
Johannes Morstein, Giovanna Romano, Belinda E. Hetzler, Ambrose Plante, Caleb Haake, Joshua Levitz, Dirk Trauner
Summary: This study develops tools for optical control of serotonin receptors, providing a new method for studying receptor function. By constructing a repeatable and reversible optical control system, this study lays the foundation for extending photopharmacology to the serotonin receptor family.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Multidisciplinary Sciences
Anat Levit Kaplan, Danielle N. Confair, Kuglae Kim, Ximena Barros-Alvarez, Ramona M. Rodriguiz, Ying Yang, Oh Sang Kweon, Tao Che, John D. McCorvy, David N. Kamber, James P. Phelan, Luan Carvalho Martins, Vladimir M. Pogorelov, Jeffrey F. DiBerto, Samuel T. Slocum, Xi-Ping Huang, Jain Manish Kumar, Michael J. Robertson, Ouliana Panova, Alpay B. Seven, Autumn Q. Wetsel, William C. Wetsel, John J. Irwin, Georgios Skiniotis, Brian K. Shoichet, Bryan L. Roth, Jonathan A. Ellman
Summary: Researchers successfully screened and synthesized molecules that can activate the 5-HT2A receptor using structure-based docking and optimization methods. These molecules exhibited potent antidepressant activity in mouse models without psychedelic effects.
Article
Chemistry, Medicinal
Bin Ma, Kevin M. Guckian, Xiao-gao Liu, Chunhua Yang, Bing Li, Robert Scannevin, Michael Mingueneau, Annabelle Drouillard, Thierry Walzer
Summary: This study discovered and optimized a novel series of potent selective S1P5 antagonists and identified an orally active brain-penetrant tool compound, providing important tools for further research on the impact of S1P5 receptors.
ACS MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Chemistry, Medicinal
Piotr Stepnicki, Katarzyna M. Targowska-Duda, Anton L. Martinez, Agata Zieba, Olga Wronikowska-Denysiuk, Martyna Z. Wrobel, Agata Bartyzel, Alicja Trzpil, Tomasz M. Wrobel, Andrzej Chodkowski, Karolina Mirecka, Tadeusz Karcz, Katarzyna Szczepanska, Maria I. Loza, Barbara Budzynska, Jadwiga Turlo, Jadwiga Handzlik, Emilia Fornal, Ewa Poleszak, Marian Castro, Agnieszka A. Kaczor
Summary: Schizophrenia is a complex mental disorder involving various neurotransmitter systems. Antipsychotics can be divided into classical drugs and atypical antipsychotics, the latter of which have a multi-target profile affecting both dopamine and serotonin receptors. This profile is considered more effective and safer in treating symptoms.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Chemistry, Medicinal
Qing Wang, Yu Zhou, Jianhui Huang, Niu Huang
Summary: Significant progress has been made in the research of the 5-HT2BR receptor since its characterization in 1992. The receptor is implicated in regulating various biological functions and diseases across different areas, with crystal complex structures providing insights for drug development.
Article
Biochemistry & Molecular Biology
Katarzyna Kucwaj-Brysz, Wesam Ali, Rafal Kurczab, Sylwia Sudol-Talaj, Natalia Wilczynska-Zawal, Magdalena Jastrzebska-Wiesek, Grzegorz Satala, Barbara Mordyl, Ewa Zeslawska, Kinga Czarnota, Gniewomir Latacz, Anna Partyka, Anna Wesolowska, Wojciech Nitek, Jadwiga Handzlik, Agnieszka-Olejarz-Maciej
Summary: This research discovered highly potent dual 5-HT6/5-HT2A receptor antagonists in a group of 1,3,5-triazine compounds, which show potential in fighting Alzheimer's disease.
BIOORGANIC CHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
Austen B. Casey, Munmun Mukherjee, Ryan P. McGlynn, Meng Cui, Stephen J. Kohut, Raymond G. Booth
Summary: This study elucidates the selective binding of novel 4-PATs compounds to 5-HT2A and 5-HT2C receptors. Ligand-receptor interactions in transmembrane domain 5 can be optimized to achieve selectivity for these compounds in antipsychotic drug development. Chirality can be exploited to attain selectivity over H-1 receptors, thereby circumventing sedative effects.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Sandra M. Martin-Guerrero, Paula Alonso, Alba Iglesias, Marta Cimadevila, Jose Brea, M. Isabel Loza, Pedro Casado, David Martin-Oliva, Pedro R. Cutillas, Javier Gonzalez-Maeso, Juan F. Lopez-Gimenez
Summary: Antipsychotic drugs induce phosphorylation of multiple pathways downstream of 5-HT2AR, and the single nucleotide polymorphism encoding 5-HT2AR-H452Y affects these drug-induced phosphorylation-dependent signaling networks.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Prithvi Hemanth, Pallavi Nistala, Vy T. T. Nguyen, Jose M. M. Eltit, Richard A. A. Glennon, Malgorzata Dukat
Summary: This study found that the affinities of 13 compounds for rat brain 5-HT2 receptors were significantly correlated with their affinities for human 5-HT2A and 5-HT2B receptors, and that the affinity of human 5-HT2A receptors was related to the lipophilicity of the 4-position substituent. Moreover, eight of the compounds exhibited agonist activity at human 5-HT2B receptors, two exhibited antagonist activity, and the affinity of human 5-HT2B receptors was correlated with the lipophilicity of the 4-position substituent. The findings suggest that the affinity of rat and human 5-HT2A receptors can be used as an indicator of the agonist activity of 2,5-DMA analogs at human 5-HT2B receptors, but cannot predict their antagonist activity. Given the presence of certain 2,5-DMA analogs on the clandestine market, their potential to produce cardiac side effects through activation of human 5-HT2B receptors following persistent or chronic use should be considered.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Nakul Ravi Raval, Annette Johansen, Lene Lundgaard Donovan, Nidia Fernandez Ros, Brice Ozenne, Hanne Demant Hansen, Gitte Moos Knudsen
Summary: This study showed that a single dose of psilocybin can lead to increased SV2A density and decreased 5-HT2AR density in the pig brain, suggesting a potential role in the antidepressant effects of psilocybin.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Anjie Xia, Xihao Yong, Changbin Zhang, Guifeng Lin, Guowen Jia, Chang Zhao, Xin Wang, Yize Hao, Yifei Wang, Pei Zhou, Xin Yang, Yue Deng, Chao Wu, Yujiao Chen, Jiawei Zhu, Xiaodi Tang, Jingming Liu, Shiyu Zhang, Jiahao Zhang, Zheng Xu, Qian Hu, Jinlong Zhao, Yuting Yue, Wei Yan, Zhaoming Su, Yuquan Wei, Rongbin Zhou, Haohao Dong, Zhenhua Shao, Shengyong Yang
Summary: This study presents the cryo-EM structures of GPR34 bound with LysoPS and its inhibition by the antagonist YL-365. The findings provide mechanistic insights into the endogenous agonist recognition and antagonist inhibition of GPR34, highlighting GPR34 as a promising target for disease treatment.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Cell Biology
Yangxia Tan, Peiyu Xu, Sijie Huang, Gong Yang, Fulai Zhou, Xinheng He, Honglei Ma, H. Eric Xu, Yi Jiang
Summary: The 5-HT5A receptor is an important protein involved in the regulation of the nervous system and a potential target for the treatment of various mental disorders. This study used cryo-electron microscopy to determine the structure of the 5-HT5A-G(i) complex and identified the ligand recognition mechanism. The findings provide valuable insights into the binding and signaling mechanisms of G(i/o)-coupled 5-HT receptors.
Article
Biochemistry & Molecular Biology
Yenthel Verhaegen, Libao Liu, Tien T. Nguyen, Tom Van Loy, Arnout R. D. Voet, Dominique Schols, Wim Dehaen, Steven De Jonghe
Summary: A diverse library of compounds was synthesized through various reactions on a bromo-naphthalene precursor, and demonstrated CCR8 antagonistic properties in experiments, with decreased activity possibly explained by homology molecular modeling.
BIOORGANIC CHEMISTRY
(2021)
Article
Neurosciences
Cristina Delgado-Sallent, Pau Nebot, Thomas Gener, Amanda B. Fath, Melina Timplalexi, M. Victoria Puig
Summary: Neural synchrony and functional connectivity are disrupted in schizophrenia. Atypical antipsychotic drugs, but not typical antipsychotic drugs, can reduce prefrontal and cortical-hippocampal hypersynchrony induced by psychosis-like states, suggesting that atypical antipsychotic drugs target prefrontal-hippocampal pathways for antipsychotic action. Serotonin receptors may play a selective role in the distinct effects of atypical antipsychotic drugs compared to typical antipsychotic drugs.
Article
Biochemistry & Molecular Biology
Charles K. Perry, Austen B. Casey, Daniel E. Felsing, Rajender Vemula, Mehreen Zaka, Noah B. Herrington, Meng Cui, Glen E. Kellogg, Clinton E. Canal, Raymond G. Booth
BIOORGANIC & MEDICINAL CHEMISTRY
(2020)
Article
Pharmacology & Pharmacy
Austen B. Casey, Munmun Mukherjee, Ryan P. McGlynn, Meng Cui, Stephen J. Kohut, Raymond G. Booth
Summary: This study elucidates the selective binding of novel 4-PATs compounds to 5-HT2A and 5-HT2C receptors. Ligand-receptor interactions in transmembrane domain 5 can be optimized to achieve selectivity for these compounds in antipsychotic drug development. Chirality can be exploited to attain selectivity over H-1 receptors, thereby circumventing sedative effects.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Neurosciences
Daniel Ryskamp Rijsketic, Austen B. Casey, Daniel A. N. Barbosa, Xue Zhang, Tuuli M. Hietamies, Grecia Ramirez-Ovalle, Matthew B. Pomrenze, Casey H. Halpern, Leanne M. Williams, Robert C. Malenka, Boris D. Heifets
Summary: This study used mice as experimental subjects to investigate the effects of environmental context on psilocybin-induced neural activity. The results showed that psilocybin increased neural activity in certain subregions of the brain while decreasing activity in others. Overall, this study demonstrated significant effects of both context and psilocybin on network architecture.
NEUROPSYCHOPHARMACOLOGY
(2023)
Article
Chemistry, Medicinal
Jessica L. Armstrong, Austen B. Casey, Tanishka S. Saraf, Munmun Mukherjee, Raymond G. Booth, Clinton E. Canal
ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE
(2020)
Review
Biochemistry & Molecular Biology
Austen B. Casey, Clinton E. Canal
ACS CHEMICAL NEUROSCIENCE
(2017)
Article
Pharmacology & Pharmacy
Paola Orlandi, Marta Banchi, Francesca Vaglini, Marco Carli, Stefano Aringhieri, Arianna Bandini, Carla Pardini, Cristina Viaggi, Michele Lai, Greta Ali, Alessandra Ottani, Eleonora Vandini, Patrizia Guidi, Margherita Bernardeschi, Veronica La Rocca, Giulio Francia, Gabriella Fontanini, Mauro Pistello, Giada Frenzilli, Daniela Giuliani, Marco Scarselli, Guido Bocci
Summary: This study investigates the role of MC4R in melanoma and the use of the selective antagonist ML in combination with vemurafenib. The results show that ML can inhibit melanoma cell proliferation and induce apoptosis through the inhibition of ERK1/2 phosphorylation and reduction of BCL-XL expression. The combination of vemurafenib and ML exhibits a synergistic effect in vitro and inhibits tumor growth in vivo without causing adverse effects.
BIOCHEMICAL PHARMACOLOGY
(2024)
Article
Pharmacology & Pharmacy
Conor J. Bloxham, Katina D. Hulme, Fabrizio Fierro, Christian Fercher, Cassandra L. Pegg, Shannon L. O'Brien, Simon R. Foster, Kirsty R. Short, Sebastian G. B. Furness, Melissa E. Reichelt, Masha Y. Niv, Walter G. Thomas
Summary: Bitter taste receptors (T2Rs) are a type of G protein-coupled receptors that allow humans to detect aversive and toxic substances. This study characterized the functional properties of previously identified T2Rs in human cardiac tissues and their naturally occurring polymorphisms. The results showed differences in signaling among different T2R variants, and revealed a potential association between the T2R50 Tyr203 variant and cardiovascular disease.
BIOCHEMICAL PHARMACOLOGY
(2024)
Article
Pharmacology & Pharmacy
Lu Chen, Huanying Shi, Wenxin Zhang, Yongjun Zhu, Haifei Chen, Zimei Wu, Huijie Qi, Jiafeng Liu, Mingkang Zhong, Xiaojin Shi, Tianxiao Wang, Qunyi Li
Summary: This study demonstrates that Carfilzomib exhibits potent anti-tumor activity against esophageal squamous cell carcinoma (ESCC) by triggering mitochondrial apoptosis and reprogramming cellular metabolism. It has been identified that activating transcription factor 3 (ATF3) plays a crucial role as a cellular target in ESCC cells treated with Carfilzomib. Overexpression of ATF3 effectively counteracts the effects of Carfilzomib on ESCC cell proliferation, apoptosis, and metabolic reprogramming. Furthermore, ATF3 mediates the anti-tumor activity of Carfilzomib, suggesting its potential as a therapeutic agent for ESCC.
BIOCHEMICAL PHARMACOLOGY
(2024)
Review
Pharmacology & Pharmacy
Xing Zhang, Xiang Li, Ran Xia, Hong-Sheng Zhang
Summary: This review summarizes recent progress on the mechanisms of ferroptosis resistance in cancer and highlights the role of redox status and metabolism. Combination therapy for ferroptosis has great potential in treating resistant malignant tumors.
BIOCHEMICAL PHARMACOLOGY
(2024)