Review
Chemistry, Medicinal
Edouard Montigne, David Balayssac
Summary: This scoping review provides an overview of studies on peripheral neuropathic pain (PNP) in rodent models, exploring compounds targeting cholinergic neurotransmission. The results highlight the potential of cholinergic compounds for the management of neuropathic pain, emphasizing the need for clinical trials.
Article
Physiology
Andriy E. Belevych, Vladimir Bogdanov, Dmitry A. Terentyev, Sandor Gyorke
Summary: Muscarinic receptors in cardiac myocytes play a critical role in regulating heart function by influencing Ca2+ handling. Reduced t-tubule density increases the sensitivity of Ca2+ release and propagation to muscarinic receptor inhibition.
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Clinical Neurology
Onella Athnaiel, Greeshma A. Job, Roberto Ocampo, Pamela Teneqexhi, William S. Messer, Michael E. Ragozzino
Summary: The study found that CDD-0102A attenuated behavioral flexibility deficits and stereotyped motor behaviors in BTBR mice, but not in B6 mice. Treatment with CDD-0102A may reduce repetitive behaviors and restricted interests in autism by stimulating striatal M-1 muscarinic receptors.
INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
(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)
Review
Psychiatry
Sofia Eickhoff, Leon Franzen, Alexandra Korda, Helena Rogg, Valerie-Noelle Trulley, Stefan Borgwardt, Mihai Avram
Summary: Alterations in the basal forebrain cholinergic nuclei are associated with cognitive impairments and symptom severity in psychotic disorders, making acetylcholine receptors a potential target for novel psychopharmacological drugs. However, many questions remain unanswered.
FRONTIERS IN PSYCHIATRY
(2022)
Review
Behavioral Sciences
Kana Okada, Kouichi Hashimoto, Kazuto Kobayashi
Summary: Object recognition memory is a fundamental memory mechanism that allows us to identify and recall various features of objects. It has been extensively studied in humans, primates, and rodents to understand the underlying neuropsychological processes involved in mammalian memory and to diagnose neurological diseases such as Alzheimer's and Parkinson's. The central cholinergic system, which is associated with cholinergic cell loss and impairment in recognition memory in the early stages of Alzheimer's, has been investigated to uncover the neural mechanisms underlying recognition memory. Previous studies have suggested that different groups of cholinergic neurons play important roles in different types of object recognition memory, such as memory for object location and object identification. Furthermore, neurodegeneration within the central cholinergic system has been found to cause deficits in object recognition memory in rodent models of Alzheimer's. Understanding how distinct cholinergic cell groups regulate various types of object recognition memory is crucial for elucidating the neuronal mechanisms of recognition memory and developing therapeutic treatments for dementia.
FRONTIERS IN BEHAVIORAL NEUROSCIENCE
(2022)
Review
Clinical Neurology
Ezio Giacobini, A. Claudio Cuello, Abraham Fisher
Summary: The review discusses the use of cholinesterase inhibitors in the treatment of Alzheimer's disease, the role of the basal forebrain cholinergic system in cognition, and potential future therapies targeting the NGF metabolic pathway and M1 muscarinic receptor. It provides an updated view of the cholinergic-oriented therapy of Alzheimer's disease and suggests new alternatives to enhance its clinical effect.
Article
Biochemistry & Molecular Biology
Chad R. Johnson, Brian D. Kangas, Emily M. Jutkiewicz, Jack Bergman, Andrew Coop
Summary: This article discusses the significant role of the cholinergic system in CNS disorders and recent advances in drug design targeting mAChRs. Despite challenges, progress has been made in developing functionally selective orthosteric and allosteric ligands with limited side effects for the treatment of diseases like Alzheimer's and schizophrenia.
Review
Biochemistry & Molecular Biology
Yu Wang, Bei Tan, Yi Wang, Zhong Chen
Summary: This review describes the role of cholinergic signaling in epilepsy, including the distribution of cholinergic neurons, muscarinic, and nicotinic receptors in the central nervous system and their relationship with neural excitability. The findings from experimental and clinical research on the role of cholinergic signaling in epilepsy are summarized, along with perspectives on future investigation to reveal the precise role of the cholinergic system in epilepsy.
Article
Neurosciences
Alan Breier, Stephen K. Brannan, Steven M. Paul, Andrew C. Miller
Summary: This study aimed to test whether trospium can mitigate cholinergic adverse events associated with xanomeline. Results showed that KarXT reduced the occurrence of cholinergic adverse events and improved safety compared to xanomeline alone.
PSYCHOPHARMACOLOGY
(2023)
Review
Neurosciences
Brian Dean, Geor Bakker, Hiroki R. Ueda, Andrew B. Tobin, Alastair Brown, Richard A. A. Kanaan
Summary: Pre-clinical models, postmortem and neuroimaging studies all suggest that muscarinic receptors are involved in the molecular pathology of schizophrenia. Clinical trials have shown that activating central muscarinic M1 and M4 receptors can reduce the severity of symptoms. This review discusses the growing evidence for the critical roles of muscarinic M1 and M4 receptors in CNS functions and their implication in schizophrenia.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2023)
Review
Physiology
Jaromir Myslivecek
Summary: Muscarinic receptors, a type of G protein-coupled receptors, have five subtypes. Researchers studying the involvement of mAChRs in various functions need to carefully choose ligands and consider the limited selectivity. This review provides an overview of off-targets, introduces the use of allosteric ligands and biased agonists, and emphasizes the importance of specific experimental designs to avoid ambiguous results.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Pharmacology & Pharmacy
Brian Dean
Summary: Schizophrenia is a syndrome that requires drugs targeting muscarinic M1 and M4 receptors, rather than dopamine D2 receptors, as antipsychotic drugs do. It would be ideal to identify individuals who respond to drugs activating the CHRM1 and 4 receptors, as non-response to treatment could be restricted to specific sub-groups within the syndrome.
EXPERT OPINION ON INVESTIGATIONAL DRUGS
(2023)
Article
Chemistry, Medicinal
Rory A. Capstick, David Whomble, Douglas L. Orsi, Andrew S. Felts, Alice L. Rodriguez, Paige N. Vinson, Sichen Chang, Anna L. Blobaum, Colleen M. Niswender, P. Jeffrey Conn, Carrie K. Jones, Craig W. Lindsley, Changho Han
Summary: The lack of suitable tool compounds has restricted the in vivo understanding of M5 receptor biology. In this article, the authors present their ongoing efforts to develop next-generation M5 antagonists with improved clearance profiles.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Chemistry, Medicinal
Douglas L. Orsi, Andrew S. Felts, Alice L. Rodriguez, Paige N. Vinson, Hyekyung P. Cho, Sichen Chang, Anna L. Blobaum, Colleen M. Niswender, Jeffrey Conn, Carrie K. Jones, Craig W. Lindsley, Changho Han
Summary: This Letter describes the ongoing effort to improve the clearance of selective M5 antagonists, reporting the replacement of the previously disclosed piperidine amide with a pyrrolidine amide core. The compounds in this series showed good potency, subtype selectivity, and moderate to low clearance profiles. Interestingly, the SAR for this series diverged from previous efforts.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2022)