keyword
https://read.qxmd.com/read/38537670/muscarinic-receptor-activators-as-novel-treatments-for-schizophrenia
#1
REVIEW
Steven M Paul, Samantha E Yohn, Stephen K Brannan, Nichole M Neugebauer, Alan Breier
Achieving optimal treatment outcomes for individuals living with schizophrenia remains challenging, despite 70 years of drug development efforts. Many chemically distinct antipsychotics have been developed over the past seven decades with improved safety and tolerability but with only slight variation in efficacy. All currently prescribed antipsychotics act as antagonists or partial agonists at the dopamine D2 receptor. With only a few possible exceptions, antipsychotic drugs have similar and modest efficacy for treating positive symptoms and are relatively ineffective in addressing the negative and cognitive symptoms of the disease...
March 25, 2024: Biological Psychiatry
https://read.qxmd.com/read/38529600/current-progress-on-central-cholinergic-receptors-as-therapeutic-targets-for-alzheimer-s-disease
#2
JOURNAL ARTICLE
Kushagra Nagori, Madhulika Pradhan, Mukesh Sharma, Ajazuddin, Hemant R Badwaik, Kartik T Nakhate
Acetylcholine (ACh) is ubiquitously present in the nervous system and has been involved in the regulation of various brain functions. By modulating synaptic transmission and promoting synaptic plasticity, particularly in the hippocampus and cortex, ACh plays a pivotal role in the regulation of learning and memory. These procognitive actions of ACh are mediated by the neuronal muscarinic and nicotinic cholinergic receptors. The impairment of cholinergic transmission leads to cognitive decline associated with aging and dementia...
March 25, 2024: Current Alzheimer Research
https://read.qxmd.com/read/38526612/a-muscarinic-receptor-antagonist-reverses-multiple-indices-of-diabetic-peripheral-neuropathy-preclinical-and-clinical-studies-using-oxybutynin
#3
RANDOMIZED CONTROLLED TRIAL
Carolina M Casselini, Henri K Parson, Katie E Frizzi, Alex Marquez, Darrell R Smith, Lucie Guernsey, Rakesh Nemmani, Alireza Tayarani, Corinne G Jolivalt, Jessica Weaver, Paul Fernyhough, Aaron I Vinik, Nigel A Calcutt
Preclinical studies indicate that diverse muscarinic receptor antagonists, acting via the M1 sub-type, promote neuritogenesis from sensory neurons in vitro and prevent and/or reverse both structural and functional indices of neuropathy in rodent models of diabetes. We sought to translate this as a potential therapeutic approach against structural and functional indices of diabetic neuropathy using oxybutynin, a muscarinic antagonist approved for clinical use against overactive bladder. Studies were performed using sensory neurons maintained in vitro, rodent models of type 1 or type 2 diabetes and human subjects with type 2 diabetes and confirmed neuropathy...
March 25, 2024: Acta Neuropathologica
https://read.qxmd.com/read/38522078/impaired-neuronal-macroautophagy-in-the-prelimbic-cortex-contributes-to-comorbid-anxiety-like-behaviors-in-rats-with-chronic-neuropathic-pain
#4
JOURNAL ARTICLE
Su Fu, Haojie Sun, Jiaxin Wang, Shuaixin Gao, Liu Zhu, Kun Cui, Shimeng Liu, Xuetao Qi, Rui Guan, Xiaocen Fan, Qingying Liu, Wen Chen, Li Su, Shuang Cui, Feifei Liao, Fengyu Liu, Catherine C L Wong, Ming Yi, You Wan
A large proportion of patients with chronic pain experience co-morbid anxiety. The medial prefrontal cortex (mPFC) is proposed to underlie this comorbidity, but the molecular and neuronal mechanisms are not fully understood. Here, we reported that impaired neuronal macroautophagy in the prelimbic cortical (PrL) subregion of the mPFC paralleled the occurrence of anxiety-like behaviors in rats with chronic spared nerve injury (SNI). Intriguingly, such macroautophagy impairment was mainly observed in a FOS/c-Fos+ neuronal subpopulation in the PrL...
March 24, 2024: Autophagy
https://read.qxmd.com/read/38521872/molecular-mechanism-of-muscarinic-acetylcholine-receptor-m3-interaction-with-gq
#5
JOURNAL ARTICLE
Donghee Ham, Asuka Inoue, Jun Xu, Yang Du, Ka Young Chung
Muscarinic acetylcholine receptor M3 (M3) and its downstream effector Gq/11 are critical drug development targets due to their involvement in physiopathological processes. Although the structure of the M3-miniGq complex was recently published, the lack of information on the intracellular loop 3 (ICL3) of M3 and extensive modification of Gαq impedes the elucidation of the molecular mechanism of M3-Gq coupling under more physiological condition. Here, we describe the molecular mechanism underlying the dynamic interactions between full-length wild-type M3 and Gq using hydrogen-deuterium exchange mass spectrometry and NanoLuc Binary Technology-based cell systems...
March 23, 2024: Communications Biology
https://read.qxmd.com/read/38520265/real-world-clinical-remission-of-severe-asthma-with-benralizumab-in-spanish-adults-with-severe-asthma
#6
JOURNAL ARTICLE
Eva Martinez-Moragon, Eusebi Chiner, Alexandra Suliana Mogrovejo, Marta Palop Cervera, Inmaculada Lluch Tortajada, Ignacio Boira Enrique, Andrés Fernando Sánchez Vera
Patients with severe eosinophilic asthma experience high risk of exacerbations and reduced quality of life. Benralizumab, a monoclonal antibody binding to IL-5 receptor α subunit, is an approved drug for its treatment. The objective was to describe clinical remission after benralizumab prescription in routine clinical practice. Retrospective multicenter study with data from four hospitals in Valencian Community (Spain) with asthma units between 2019 and 2020. Data was gathered at baseline and after 12 months...
March 23, 2024: Journal of Asthma
https://read.qxmd.com/read/38513777/elucidation-of-active-components-and-target-mechanism-in-jinqiancao-granules-for-the-treatment-of-prostatitis-and-benign-prostatic-hyperplasia
#7
JOURNAL ARTICLE
Han Zhou, Tao Hou, Aijin Shen, Wenyi Yu, Liangliang Zhou, Wenjie Yuan, Wanxian Wang, Yumin Yao, Jixia Wang, Yanfang Liu, Xinmiao Liang
ETHNOPHARMACOLOGICAL RELEVANCE: Prostatitis and benign prostatic hyperplasia (BPH) are inflammations of the prostate gland, which surrounds the urethra in males. Jinqiancao granules are a traditional Chinese medicine used to treat kidney stones and this medicine consists of four herbs: Desmodium styracifolium (Osbeck) Merr., Pyrrosia calvata (Baker) Ching, Plantago asiatica L. and stigma of Zea mays L. AIM OF THE STUDY: We hypothesized that Jinqiancao granules could be a potential therapy for prostatitis and BPH, and this work aimed to elucidate active compounds in Jinqiancao granules and their target mechanisms for the potential treatment of the two diseases...
March 19, 2024: Journal of Ethnopharmacology
https://read.qxmd.com/read/38510900/irinotecan-induced-transient-dysarthria-in-a-patient-with-metastatic-colorectal-cancer-a-case-report
#8
Kim Alfred E Inting, Anthony N Piano
We present a rare case of irinotecan-induced transient dysarthria in a 60-year-old female undergoing FOLFIRI (folinic acid (leucovorin), fluorouracil (5-FU), and irinotecan) chemotherapy for metastatic colorectal cancer. In eight out of the 12 cycles, an isolated, self-limiting "lingual dysarthria" with tongue stiffness consistently occurred during infusion and resolved promptly upon completion. Cranial imaging done during the initial episode and after the completion of the chemotherapy regimen were unremarkable...
February 2024: Curēus
https://read.qxmd.com/read/38505261/editorial-proteins-and-protein-complexes-underlying-mitochondrial-structure-function-and-metabolism-implications-in-diseases
#9
EDITORIAL
Mohammad Golam Sabbir, Nawab John Dar, Shahnawaz Ali Bhat, Hamad H Alanazi, Jeff Perry
No abstract text is available yet for this article.
2024: Frontiers in Cell and Developmental Biology
https://read.qxmd.com/read/38503897/antiemetic-activity-of-abietic-acid-possibly-through-the-5ht-3-and-muscarinic-receptors-interaction-pathways
#10
JOURNAL ARTICLE
Rubel Hasan, Abdulrahman Alshammari, Norah A Albekairi, Md Shimul Bhuia, Meher Afroz, Raihan Chowdhury, Muhammad Ali Khan, Siddique Akber Ansari, Irfan Aamer Ansari, Mohammad S Mubarak, Muhammad Torequl Islam
The present study was designed to evaluate the antiemetic activity of abietic acid (AA) using in vivo and in silico studies. To assess the effect, doses of 50 mg/kg b.w. copper sulfate (CuSO4 ⋅5H2 O) were given orally to 2-day-old chicks. The test compound (AA) was given orally at two doses of 20 and 40 mg/kg b.w. On the other hand, aprepitant (16 mg/kg), domperidone (6 mg/kg), diphenhydramine (10 mg/kg), hyoscine (21 mg/kg), and ondansetron (5 mg/kg) were administered orally as positive controls (PCs)...
March 19, 2024: Scientific Reports
https://read.qxmd.com/read/38501194/g-protein-coupled-receptor-mediated-autophagy-in-health-and-disease
#11
REVIEW
Devrim Öz-Arslan, Zeynep Aslıhan Durer, Beki Kan
G protein-coupled receptors (GPCRs) constitute the largest and most diverse superfamily of mammalian transmembrane proteins. These receptors are involved in a wide range of physiological functions and are targets for more than a third of available drugs in the market. Autophagy is a cellular process involved in degrading damaged proteins and organelles and in recycling cellular components. Deficiencies in autophagy are involved in a variety of pathological conditions. Both GPCRs and autophagy are essential in preserving homeostasis and cell survival...
March 19, 2024: British Journal of Pharmacology
https://read.qxmd.com/read/38500748/in-vitro-evaluation-of-pet-radiotracers-for-imaging-synaptic-density-the-acetylcholine-transporter-ampa-tarp-%C3%AE-8-and-muscarinic-m4-receptors-in-alzheimer-s-disease
#12
JOURNAL ARTICLE
Faustine d'Orchymont, Andrea Narvaez, Roger Raymond, Pallavi Sachdev, Arnaud Charil, Stephen Krause, Neil Vasdev
Several therapeutics and biomarkers that target Alzheimer's disease (AD) are under development. Our clinical positron emission tomography (PET) research programs are interested in six radiopharmaceuticals to image patients with AD and related dementias, specifically [11 C]UCB-J and [18 F]SynVesT-1 for synaptic vesicle glycoprotein 2A as a marker of synaptic density, two vesicular acetylcholine transporter PET radiotracers: [18 F]FEOBV and [18 F]VAT, as well as the transmembrane AMPA receptor regulatory protein (TARP)-γ8 tracer, [18 F]JNJ-64511070, and the muscarinic acetylcholine receptor (mAChR) M4 tracer [11 C]MK-6884...
2024: American Journal of Nuclear Medicine and Molecular Imaging
https://read.qxmd.com/read/38500741/in-vitro-evaluation-of-pet-radiotracers-reflecting-multidimensionality-of-alzheimer-s-disease-building-more-roadmaps-for-clinical-translation
#13
EDITORIAL
Yingfang He, Fang Xie
In the current issue of American Journal of Nuclear Medicine and Molecular Imaging, Vasdev et al. presented a work entitled "In Vitro Evaluation of PET Radiotracers for Imaging Synaptic Density, the Acetylcholine Transporter, AMPA-tarp-γ8 and Muscarinic M4 receptors in Alzheimer's disease". In which, in vitro autoradiography studies using radioligands were employed as a valuable tool to gain more insights for potential clinical translation. In this invited perspective, we would like to briefly introduce the current state of AD diagnosis, especially PET imaging on synapse, and highlight the advances of PET imaging in pre-clinic and clinic that might assist on precise therapy in the future...
2024: American Journal of Nuclear Medicine and Molecular Imaging
https://read.qxmd.com/read/38499061/activated-non-neuronal-cholinergic-system-correlates-with-non-type-2-inflammation-and-exacerbations-in-severe-asthma
#14
JOURNAL ARTICLE
Dan Huang, Li Zhang, Ying Liu, Ji Wang, Jie Zhang, Katherine J Baines, Gang Liu, Alan Chen-Yu Hsu, Fang Wang, Zhihong Chen, Brian G Oliver, Min Xie, Ling Qin, Dan Liu, Huajing Wan, Fengming Luo, Weimin Li, Gang Wang, Peter G Gibson
BACKGROUND: Non-neuronal cholinergic system (NNCS) contributes to various inflammatory airway diseases. However, the role of NNCS in severe asthma (SA) remains largely unexplored. OBJECTIVE: To explore airway NNCS in SA. METHODS: In this prospective cohort study based on the Australasian Severe Asthma Network in a real-world setting, patients with SA (n=52) and non-SA (n=104) underwent clinical assessment and sputum induction. The mRNA levels of NNCS components and proinflammatory cytokines in sputum were detected using RT-qPCR, and the concentrations of acetylcholine (Ach)-related metabolites were examined using LC-MS/MS...
March 16, 2024: Annals of Allergy, Asthma & Immunology
https://read.qxmd.com/read/38498544/vasodilation-and-blood-pressure-lowering-effect-of-3-demethyl-2-geranyl-4-prenylbellidifoline-a-xanthone-obtained-from-garcinia-achachairu-in-hypertensive-rats
#15
JOURNAL ARTICLE
Luísa Nathália Bolda Mariano, Rita de Cássia Vilhena da Silva, Rivaldo Niero, Valdir Cechinel Filho, José Eduardo da Silva-Santos, Priscila de Souza
3-demethyl-2-geranyl-4-prenylbellidifoline (DGP), a natural xanthone isolated from Garcinia achachairu , has previously demonstrated remarkable diuretic and renal protective actions. The present study expands its actions on the cardiovascular system by evaluating its vasorelaxant and blood pressure-lowering effects in spontaneously hypertensive rats (SHRs). Aortic endothelium-intact (E+) preparations of SHRs pre-contracted by phenylephrine and exposed to cumulative concentrations of G. achachairu extract, fractions, and DGP exhibited a significant relaxation compared to vehicle-only exposed rings...
February 15, 2024: Plants (Basel, Switzerland)
https://read.qxmd.com/read/38495977/analysing-the-effect-caused-by-increasing-the-molecular-volume-in-m1-achr-receptor-agonists-and-antagonists-a-structural-and-computational-study
#16
JOURNAL ARTICLE
Wilber Montejo-López, Raúl Sampieri-Cabrera, María Inés Nicolás-Vázquez, Juan Manuel Aceves-Hernández, Rodrigo Said Razo-Hernández
M1 muscarinic acetylcholine receptor (M1-AChR), a member of the G protein-coupled receptors (GPCR) family, plays a crucial role in learning and memory, making it an important drug target for Alzheimer's disease (AD) and schizophrenia. M1-AChR activation and deactivation have shown modifying effects in AD and PD preclinical models, respectively. However, understanding the pharmacology associated with M1-AChR activation or deactivation is complex, because of the low selectivity among muscarinic subtypes, hampering their therapeutic applications...
March 14, 2024: RSC Advances
https://read.qxmd.com/read/38491847/functional-neuroanatomy-of-basal-forebrain-projections-to-the-basolateral-amygdala-transmitters-receptors-and-neuronal-subpopulations
#17
REVIEW
Alexander Joseph McDonald
The projections of the basal forebrain (BF) to the hippocampus and neocortex have been extensively studied and shown to be important for higher cognitive functions, including attention, learning, and memory. Much less is known about the BF projections to the basolateral nuclear complex of the amygdala (BNC), although the cholinergic innervation of this region by the BF is actually far more robust than that of cortical areas. This review will focus on light and electron microscopic tract-tracing and immunohistochemical (IHC) studies, many of which were published in the last decade, that have analyzed the relationship of BF inputs and their receptors to specific neuronal subtypes in the BNC in order to better understand the anatomical substrates of BF-BNC circuitry...
March 2024: Journal of Neuroscience Research
https://read.qxmd.com/read/38477292/pet-imaging-of-m4-muscarinic-acetylcholine-receptors-in-rhesus-macaques-using-11-c-mk-6884-quantification-with-kinetic-modeling-and-receptor-occupancy-by-cvl-231-emraclidine-a-novel-positive-allosteric-modulator
#18
JOURNAL ARTICLE
Vasily Belov, Nicolas J Guehl, Sridhar Duvvuri, Philip Iredale, Sung-Hyun Moon, Maeva Dhaynaut, Srinivas Chakilam, Alexander C MacDonagh, Peter A Rice, Daniel L Yokell, John J Renger, Georges El Fakhri, Marc D Normandin
Stimulation of the M4 muscarinic acetylcholine receptor reduces striatal hyperdopaminergia, suggesting its potential as a therapeutic target for schizophrenia. Emraclidine (CVL-231) is a novel, highly selective, positive allosteric modulator (PAM) of M4 muscarinic acetylcholine receptors i.e. acts as a modulator that increases the response of these receptors. First, we aimed to further characterize the positron emission tomography (PET) imaging and quantification performance of a recently developed M4 PAM radiotracer, [11 C]MK-6884, in non-human primates (NHPs)...
March 13, 2024: Journal of Cerebral Blood Flow and Metabolism
https://read.qxmd.com/read/38464273/nir1-lns2-is-a-novel-phosphatidic-acid-biosensor-that-reveals-mechanisms-of-lipid-production
#19
Claire C Weckerly, Taylor A Rahn, Max Ehrlich, Rachel C Wills, Joshua G Pemberton, Michael V Airola, Gerald R V Hammond
Despite various roles of phosphatidic acid (PA) in cellular functions such as lipid homeostasis and vesicular trafficking, there is a lack of high-affinity tools to study PA in live cells. After analysis of the predicted structure of the LNS2 domain in the lipid transfer protein Nir1, we suspected that this domain could serve as a novel PA biosensor. We created a fluorescently tagged Nir1-LNS2 construct and then performed liposome binding assays as well as pharmacological and genetic manipulations of HEK293A cells to determine how specific lipids affect the interaction of Nir1-LNS2 with membranes...
February 28, 2024: bioRxiv
https://read.qxmd.com/read/38463995/%C3%AE-7-nicotinic-acetylcholine-receptors-are-necessary-for-basal-forebrain-activation-to-increase-expression-of-the-nerve-growth-factor-receptor-trka
#20
Jacob Kumro, Ashutosh Tripathi, Alvin V Terry, Anilkumar Pillai, David T Blake
Activation of the basal forebrain leads to increases in the expression of the nerve growth factor receptor, Tropomyosin receptor kinase A (TrkA) and decreases in expression of the beta amyloid cleavage enzyme 1 (BACE1) in the cerebral cortex of both sexes of 5xFAD mice. The studies described in this report were designed to determine if these changes were dependent on acetylcholine receptors. Mice were stimulated unilaterally in the basal forebrain for two weeks. Animals were administered a cholinergic antagonist, or saline, 30 minutes prior to stimulation...
March 3, 2024: bioRxiv
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