Article
Biochemistry & Molecular Biology
Nyanbol Kuol, Majid Davidson, Jimsheena Karakkat, Rhiannon T. Filippone, Margaret Veale, Rodney Luwor, Sarah Fraser, Vasso Apostolopoulos, Kulmira Nurgali
Summary: Tumor cells express immunosuppressive molecules and produce acetylcholine, which contribute to tumor evasion and development. Blocking M3R inhibits tumor growth and suppresses immunosuppressive molecules and angiogenesis through the AKT/ERK signaling pathway, leading to an improved immune response against cancer. The expression of immunosuppressive and cholinergic markers may have potential in determining prognosis and treatment strategies for colorectal cancer patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Medicine, General & Internal
Ryusei Satoh, Kiyoharu Kawakami, Kazuhiko Nakadate
Summary: In recent years, the use of smart drugs to enhance concentration and memory learning skills has become increasingly common. However, the effectiveness of these drugs in healthy individuals has not been confirmed. This study focused on the long-term effects of smart drugs on neural circuits, specifically in the hippocampus where acetylcholine plays a role in memory learning.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Neurosciences
Paola Palombo, Sheila Antonagi Engi, Thais Suemi Yokoyama, Andreia Gomes Bezerra, Daniela Fernandez Curado, Augusto Anesio, Rodrigo Molini Leao, Paulo Caleb Junior de Lima Santos, Fabio Cardoso Cruz, Jose Carlos F. Galduroz
Summary: The study found that biperiden can modulate the effects of alcohol reward possibly through changing dopamine and cholinergic mesolimbic neurotransmission. Different doses of biperiden blocked ethanol-induced conditioned place preference and increased the number of Fos-positive cells and dopamine turnover in the nucleus accumbens without affecting motor coordination.
NEUROSCIENCE LETTERS
(2021)
Article
Biochemistry & Molecular Biology
Nathalia M. Pinheiro, Rosana Banzato, Iolanda Tiberio, Marco A. M. Prado, Vania F. Prado, Ayman K. Hamouda, Carla M. Prado
Summary: In acute lung injury, inflammatory markers are significantly elevated in cholinergic-deficient mice compared to wild-type, but treatment with the selective alpha 7 nicotinic receptor agonist PNU 282987 can restore the response and reduce lung inflammation. The anti-inflammatory effects of the lung cholinergic system are associated with an increase in the level of alpha 7 nicotinic receptors, suggesting potential clinical applications for treating acute lung injury.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Chemistry, Medicinal
Jing-Jing Zhang, Hualong Fu, Ruofan Lin, Jingyin Zhou, Ahmed Haider, Weiwei Fang, Nehal H. Elghazawy, Jian Rong, Jiahui Chen, Yinlong Li, Chongzhao Ran, Thomas L. Collier, Zhen Chen, Steven H. Liang
Summary: Cholinergic receptors are important targets for diagnosis and treatment of cognitive decline and cardiovascular impairment. Positron emission tomography (PET) has been used to study the roles and functions of these receptors in disease development. Recent progress has been made in the development of PET probes targeting cholinergic receptors, including ligand structure, radiochemistry, pharmacology, and in vivo performance. This review provides a comprehensive overview of the current state-of-the-art PET probes for cholinergic receptors, including their design, synthesis, and evaluation in preclinical and clinical settings.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Oncology
Nina A. Hering, Verena Liu, Rayoung Kim, Benjamin Weixler, Raoul A. Droeser, Marco Arndt, Ioannis Pozios, Katharina Beyer, Martin E. Kreis, Hendrik Seeliger
Summary: Darifenacin, a selective M3R antagonist, inhibits the growth and invasion of colon carcinoma cells in vitro and in vivo, suggesting it may be a beneficial treatment for colorectal cancer. Targeting cholinergic signaling via M3R by darifenacin could be a promising addition to systemic therapy for CRC patients expressing M3R.
Review
Pharmacology & Pharmacy
Masato Mashimo, Koichiro Kawashima, Takeshi Fujii
Summary: Immune cells express various components of the cholinergic system, influencing immune function. The expression of mAChR subtypes and nAChR subunits varies depending on tissue and immune status. Modulation of immune function can be achieved through cholinergic pathways impacting T and B cell activity.
BIOLOGICAL & PHARMACEUTICAL BULLETIN
(2022)
Article
Radiology, Nuclear Medicine & Medical Imaging
Jakob Albrecht, Samantha Exner, Carsten Groetzinger, Sonal Prasad, Frank Konietschke, Nicola Beindorff, Anja A. Kuhl, Vikas Prasad, Winfried Brenner, Eva J. Koziolek
Summary: Peptide receptor radionuclide therapy (PRRT) using radiolabeled somatostatin receptor (SSTR) analogs is a common approach in advanced neuroendocrine neoplasms. Recently, SSTR antagonists have shown promising results for imaging and therapy due to a higher number of binding sites than in commonly used agonists. Lu-177-DOTA-JR11 exhibited a higher tumor-to-kidney ratio, increased G2/M phase accumulation of cells, decreased tumor size, prolonged median survival, and stable tumor uptake over 2 treatment cycles compared to Lu-177-DOTATOC.
JOURNAL OF NUCLEAR MEDICINE
(2021)
Article
Radiology, Nuclear Medicine & Medical Imaging
Kevin P. Labadie, Donald K. Hamlin, Aimee Kenoyer, Sara K. Daniel, Alan F. Utria, Andrew D. Ludwig, Heidi L. Kenerson, Lily Li, Jonathan G. Sham, Delphine L. Chen, Johnnie J. Orozco, Raymond S. Yeung, Chris Orvig, Yawen Li, D. Scott Wilbur, James O. Park
Summary: This study describes the development and efficacy of a Th-227-labeled GPC3-targeting antibody conjugate (Th-227-octapa-alpha GPC3) for treating HCC. The results show that the treatment is stable in vitro, exhibits high specificity for GPC3, and significantly reduces tumor burden in an orthotopic murine model of HCC without causing acute off-target toxicity.
JOURNAL OF NUCLEAR MEDICINE
(2022)
Article
Neurosciences
Richa Awasthi, Naveen Chandra, Edi Barkai
Summary: Training rats in an olfactory discrimination task can accelerate learning and this is maintained at the cellular level by reducing the conductance of a specific current in the brain. This reduction is associated with enhanced repetitive action potential firing. The study explores the role of membrane phosphatidylinositol 4,5-bisphosphate and potassium channels in this process, suggesting that rule learning-induced enhancement in intrinsic neuronal excitability is mediated by reduced conductance of potassium channels.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Pharmacology & Pharmacy
Huaye Gao, Jintong Li, Xiaoping Chen, Zhanguo Sun, Gang Cui, Minlu Cheng, Li Ding
Summary: 101BHG-D01 is a novel drug for the treatment of COPD, which has acceptable pharmacokinetics, metabolism, and safety profile.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Pin-Kuei Fu, Yu-Feng Wei, Chau-Chyun Sheu, Chen-Yu Wang, Chi-Kuei Hsu, Chia-Min Chen, Wei-Chih Chen, Kuang-Yao Yang
Summary: This study investigated the effects of tiotropium bromide soft mist inhalers on lung mechanics and gas exchange in COPD patients receiving mechanical ventilation. The results showed a significant reduction in respiratory resistance within 6 hours of administration, as well as a significant improvement in the oxygenation index at 24 hours. Further studies should explore whether increasing dosage or frequency can enhance the bronchodilation effect.
Article
Chemistry, Analytical
Huaye Gao, Minlu Cheng, Haijun Liu, Li Ding
Summary: 101BHG-D01 is a novel, long-acting and selective muscarinic receptor antagonist used for the treatment of chronic obstructive pulmonary disease (COPD) and rhinorrhea in rhinitis. Liquid chromatography tandem mass spectrometry (LC-MS/MS) methods were developed to quantify 101BHG-D01 and its metabolite M6 in human plasma, urine and feces. These validated methods were successfully applied in a clinical study in Chinese subjects, providing important pharmacokinetic information.
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
(2023)
Article
Oncology
Manja Friese-Hamim, Anderson Clark, Dominique Perrin, Lindsey Crowley, Christof Reusch, Olga Bogatyrova, Hong Zhang, Timothy Crandall, Jing Lin, Jianguo Ma, David Bachner, Jurgen Schmidt, Martin Schaefer, Christopher Stroh
Summary: This study reports on a potential central nervous system-penetrant MET inhibitor that demonstrates intracranial efficacy against non-small cell lung cancer brain metastases. The research confirms the inhibitory effect of the drug on brain metastases in animal models and suggests that the intracranial antitumor activity is independent of blood-brain barrier leakiness.
Article
Chemistry, Medicinal
Hari K. Namballa, Michael Dorogan, Ashok R. Gudipally, Sunday Okafor, Satishkumar Gadhiya, Wayne W. Harding
Summary: We evaluated alkoxylated and dialkoxylated (-)-stepholidine analogues at the C-3 and C-9 positions of the THPB template for their affinity towards dopamine receptors. A C-9 ethoxyl substituent showed optimal D1R affinity, with larger C-9 substituents decreasing affinity. Novel ligands with nanomolar affinities for D1R and no affinity for D2R or D3R were identified, including compound 12a as a D1R antagonist for both G-protein- and β-arrestin-based signaling, and compound 23b as the most potent and selective D3R ligand to date.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)