Article
Chemistry, Medicinal
Ramakrishna Nirogi, Abdul Rasheed Mohammed, Anil Karbhari Shinde, Shankar Reddy Gagginapally, Durga Malleshwari Kancharla, Srinivasa Rao Ravella, Narsimha Bogaraju, Vanaja Reddy Middekadi, Ramkumar Subramanian, Raghava Choudary Palacharla, Vijay Benade, Nageswararao Muddana, Renny Abraham, Rajesh Babu Medapati, Jagadeesh Babu Thentu, Venkat Reddy Mekala, Surendra Petlu, Bujji Babu Lingavarapu, Sivasekhar Yarra, Narendra Kagita, Vinod Kumar Goyal, Santosh Kumar Pandey, Venkat Jasti
Summary: A novel 5-HT4R partial agonist was synthesized and demonstrated significant nonclinical cognitive efficacy, as well as potential disease-modifying properties. Phase 1 and Phase 2 clinical studies confirmed therapeutic effects of the drug with no major safety concerns for long-term use.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
J. Daniel Bailey, Edward Helbling, Amey Mankar, Matthew Stirling, Fred Hicks, David K. Leahy
Summary: Reducing or eliminating organic solvent use in pharmaceutical manufacturing is a highly effective way to reduce environmental, health, and safety impacts. The process described utilizing primarily water-based methods significantly reduces material inputs and organic solvent use, while surprisingly using less water and improving overall yield compared to traditional methods.
Article
Pharmacology & Pharmacy
Dae Young Lee, Hee Eun Kang
Summary: This study validated a quantitative assay for DA-6886 in rat plasma and evaluated its pharmacokinetics and tissue distribution in rats. The results showed that DA-6886 distributed extensively in the liver, kidney, lung, and digestive tract, and exhibited nonlinear pharmacokinetics after oral administration.
Article
Biochemistry & Molecular Biology
Alejandro Castro-Alvarez, Emigdio Chavez-Angel, Ronald Nelson
Summary: This study analyzed a series of active compounds in the 5-HT4 receptor using quantitative structure-activity relationship, leading to the design of novel 5-HT4 partial agonists with potential biological activity. The research provided new insights for the design and development of new therapeutic options for neurodegenerative disorders like Alzheimer's disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Pharmacology & Pharmacy
Ulrich Gergs, Tobias Brueckner, Britt Hofmann, Joachim Neumann
Summary: The study revealed that lowering temperature can increase arrhythmias in mice overexpressing the human 5-HT4 receptor in their cardiac myocytes, suggesting a potential link between 5-HT4 receptors and hypothermia-induced arrhythmias in human patients.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Neurosciences
Pierre Lecouflet, Candice M. Roux, Brigitte Potier, Marianne Leger, Elie Brunet, Jean-Marie Billard, Pascale Schumann-Bard, Thomas Freret
Summary: Activation of the 5-HT4R has been shown to impact LTP within the hippocampal CA1 area through modulation of GABAergic neurotransmission. The study also revealed the involvement of GABA(B) receptor in this regulatory process.
Article
Gastroenterology & Hepatology
John R. Konen, Melody M. Haag, Daria Guseva, Molly Hurd, Alisha A. Linton, Brigitte Lavoie, Colleen B. Kerrigan, Emily Joyce, Stephan C. Bischoff, Steve Swann, Luana Griffin, Jun Matsukawa, Matthew D. Falk, Tony S. Gibson, Grant W. Hennig, Jill Wykosky, Gary M. Mawe
Summary: Stimulation of epithelial 5-HT(4)Rs can enhance propulsive motility, indicating mucosal 5-HT(4)Rs may represent a safe and effective therapeutic target for constipation treatment.
NEUROGASTROENTEROLOGY AND MOTILITY
(2021)
Article
Biochemistry & Molecular Biology
Ulrich Gergs, Timo Gerigk, Jonas Wittschier, Constanze T. Schmidbaur, Clara Rottger, Mareen Mahnkopf, Hanna Edler, Hartmut Wache, Joachim Neumann
Summary: The study found that cardiac function is affected by 5-HT4 receptor overexpression under pathophysiological conditions, with potential benefits or drawbacks depending on the type of stress. 5-HT4 receptor overexpression influenced the response of the heart to hypoxia and ischemia, as well as cardiac hypertrophy.
Article
Biochemistry & Molecular Biology
Hannes Jacob, Pauline Braekow, Rebecca Schwarz, Christian Hoehm, Uwe Kirchhefer, Britt Hofmann, Joachim Neumann, Ulrich Gergs
Summary: Ergotamine is a tryptamine-related alkaloid used to treat migraines. It has positive inotropic effects on both 5-HT4-serotonin receptors and H-2-histamine receptors in the human heart.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Eri Kitayama, Maki Kimura, Takehito Ouchi, Masahiro Furusawa, Yoshiyuki Shibukawa
Summary: This study investigated the dynamics of intracellular cAMP in cultured human odontoblasts to understand the detailed expression patterns and role of the intracellular cAMP signaling pathway. The results showed the presence of G(alpha)s protein and various receptors (IP, 5-HT4, D-1, A(2A), and VIP) in odontoblasts. Activation of these receptors increased intracellular cAMP levels by activating AC, and this increase was inhibited by an AC inhibitor and receptor antagonists.
Review
Gastroenterology & Hepatology
James J. Galligan
Summary: 5-HT4 receptors are G protein-coupled receptors that activate adenylate cyclase to increase intracellular cyclic AMP levels, leading to the activation of protein kinase A. These receptors are expressed in the central and peripheral nervous systems, particularly in the enteric nervous system, where they enhance neurotransmitter release and propulsive motility. Novel 5-HT4 receptor agonists, 5-HT4-LA1 and 5-HT4-LA-2, stimulate colonic motility locally without being absorbed systemically, demonstrating prokinetic actions in the GI tract.
NEUROGASTROENTEROLOGY AND MOTILITY
(2021)
Article
Pharmacology & Pharmacy
Shayma El-Atawneh, Amiram Goldblum
Summary: In recent years, the cannabinoid type 2 receptor (CB2R) has emerged as a major target for treating various diseases. The development of multitargeting agents (MTAs) has gained attention as a promising approach, and ligand-based modeling has proven to be a better starting point for molecular discovery than docking. The study focuses on designing single multitargeting agents for CB2R and other targets, such as CB1R, PPAR gamma, and 5-HT4R, and explores their potential for treating Inflammatory Bowel Disease (IBD).
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Medicine, Research & Experimental
Xiaoling Xie, Wanwen Yang, Wuju Zhang, Yingqi Qiu, Zeyou Qiu, Hao Wang, Yuxing Hu, Yuhua Li, Xuan Zhou, Luyao Li, Zhuanzhuan Chen, Chenbo Zhao, Yao Lu, Keqin Zhang, Eryong Lai, Xiaochun Bai
Summary: This study identifies tegaserod maleate as a potential therapeutic agent for acute myeloid leukemia (AML) by targeting TRPM8. TRPM8 plays a crucial role in leukemogenesis and its inhibition promotes apoptosis in AML cells. The study also reveals that TRPM8 regulates the ERK-CREB/c-Fos signaling axis. Overexpression of TRPM8 is observed in AML patients, suggesting its prognostic value in AML.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Neurosciences
Angharad N. de Cates, Marieke A. G. Martens, Lucy C. Wright, Daisy Gibson, Gershon Spitz, Cassandra D. Gould van Praag, Sana Suri, Philip J. Cowen, Susannah E. Murphy, Catherine J. Harmer
Summary: This study found that the 5-HT4 receptor agonist prucalopride enhanced functional connectivity between regions involved in cognitive networks and reduced connectivity within the default mode network in healthy volunteers. This may explain the previously observed cognitive enhancement effects of 5-HT4 receptor agonists in humans and supports their potential use in clinical psychiatric populations.
BIOLOGICAL PSYCHIATRY-COGNITIVE NEUROSCIENCE AND NEUROIMAGING
(2023)
Article
Pharmacology & Pharmacy
Ulrich Gergs, Hannes Jacob, Pauline Braekow, Britt Hofmann, Steffen Pockes, Laura J. Humphrys, Uwe Kirchhefer, Charlotte Fehse, Joachim Neumann
Summary: We investigated the effects of LSD on the heart and found that it can increase the contractile force and beating rate of the atria. These effects may be mediated by the 5-HT4 receptor and H-2 histamine receptor.
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
(2023)