Cobenfy (xanomeline)
Research Synopsis
- Recent research shows that Cobenfy (xanomeline) acts as a selective muscarinic receptor agonist primarily targeting M1 receptors, offering new hope for treating conditions like Alzheimer's disease and Tourette syndrome.
- In animal studies, xanomeline demonstrated effectiveness in reducing tic-like behaviors in murine models of Tourette syndrome by activating M1 muscarinic receptors.
- A study indicated that xanomeline enhances the release of soluble amyloid precursor proteins, suggesting it could play a role in reducing amyloid plaque formation in Alzheimer's patients.
- Several pharmacokinetic studies have successfully developed sensitive methods for measuring xanomeline and its metabolites in human plasma, providing valuable tools for clinical research.
- Clinical trials revealed that xanomeline improved cognitive function and behavioral symptoms in Alzheimer's patients, although there was a notable higher incidence of gastrointestinal side effects, leading to significant discontinuation rates in higher dose groups.
- Xanomeline's unique profile shows it has minimal side effects compared to other muscarinic agonists, such as reduced salivation and tremors, which are common with similar medications.
- The drug's ability to influence dopamine release without altering acetylcholine levels suggests potential for treating cognitive disorders without typical cholinergic side effects.
- PET imaging studies demonstrated xanomeline’s rapid brain penetration and potential for therapeutic effects, indicating a favorable safety profile for further clinical exploration.
- Ongoing research emphasizes the need for careful consideration of dosing to balance efficacy and tolerability, particularly in frail populations like Alzheimer’s patients.
- Overall, xanomeline presents a promising pathway for the development of targeted therapies for cognitive impairments and related disorders, meriting further investigation in clinical settings.
Cobenfy (xanomeline)
Activation of M muscarinic receptors in the striatum reduces tic-like behaviours in two distinct murine models of Tourette syndrome.
London, UK
2 hours ago
1 Received
- Researchers are looking for new treatments for Tourette syndrome (TS) because current medicines don't work well and can have bad side effects.
- They experimented with a special drug called xanomeline on mice that have TS-like behaviors to see if it could help reduce tics.
- The results showed that xanomeline was effective, especially by targeting certain receptors in the brain, suggesting it could be a new way to treat TS in humans.
$100 - $150
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Novel functional M1 selective muscarinic agonists. Synthesis and structure-activity relationships of 3-(1,2,5-thiadiazolyl)-1,2,5,6-tetrahydro-1-methylpyridines .
London, UK
2 hours ago
1 Received
- A series of substituted tetrahydro-1-methylpyridines were synthesized and tested for their ability to bind to central muscarinic cholinergic receptors, specifically M1, M2, and M3, using specific radiolabeled ligands.
- The study revealed that certain alkoxy derivatives displayed strong binding affinity, with a notable U-shaped relationship between the chain length of alkoxy groups and receptor binding potency.
- Compounds with alkylthio substitutions demonstrated higher receptor affinity and potency compared to their alkoxy counterparts, while some alkyl derivatives showed significantly lower affinity for central muscarinic receptors.
$100 - $150
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Sensitive liquid chromatographic method for the determination of a specific M1 agonist, LY246708, an investigational agent with potential for the treatment of Alzheimer's disease, in human plasma.
London, UK
2 hours ago
1 Received
- A reversed-phase HPLC method was developed to measure the new M1 agonist LY246708 in human plasma.
- The process involves extracting the compound and a standard using hexane, evaporating the solvent, and reconstituting the residue in a specific mobile phase for analysis.
- The method showed a low detection limit of 1.5 ng/ml, linear response, and proved to be reliable and robust for use in various labs and pharmacokinetic studies.
$100 - $150
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Xanomeline: a novel muscarinic receptor agonist with functional selectivity for M1 receptors.
London, UK
2 hours ago
1 Received
- Xanomeline is a selective muscarinic receptor agonist that shows high affinity for M1 receptors, while having little to no effect on other neurotransmitter receptors.
- In experimental settings, xanomeline enhances phospholipid hydrolysis in certain cell types and influences dopamine release in the striatum without affecting acetylcholine levels.
- Unlike other muscarinic agonists, xanomeline improves heart rate but does not cause common side effects like salivation or tremor, highlighting its unique functional selectivity.
$100 - $150
Hourly Rate
Neurochemical effects of the M1 muscarinic agonist xanomeline (LY246708/NNC11-0232).
London, UK
2 hours ago
1 Received
- Xanomeline, a compound studied in rats, increases dopamine metabolite levels (DOPAC) in the striatum, indicating its influence on dopamine turnover.
- The increase in DOPAC is blocked by the M1 antagonist trihexyphenidyl, suggesting that xanomeline interacts specifically with M1 receptors on dopamine nerve terminals.
- Additionally, xanomeline does not affect certain acetylcholine receptors, as it does not induce salivation and shows selectivity for M1 receptors without interfering with M2 or M3 receptor functions.
$100 - $150
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Determination of xanomeline in human plasma by ion-spray tandem mass spectrometry.
London, UK
2 hours ago
1 Received
- Xanomeline is a drug being tested in phase II trials for Alzheimer's disease, acting as a muscarinic receptor agonist.
- A new assay using ion-spray tandem mass spectrometry was created to accurately measure xanomeline levels in plasma by extracting it into hexane.
- The method shows a linear detection range from 0.075 to 5.0 ng/mL of xanomeline with a quick sample run time of 2.5 minutes per injection.
$100 - $150
Hourly Rate
The utility of salivary amylase as an evaluation of M3 muscarinic agonist activity in Alzheimer's disease.
London, UK
2 hours ago
1 Received
- A phase I study tested the safety and tolerance of two doses of xanomeline tartrate (100 mg and 115 mg) in 12 Alzheimer's disease (AD) patients, focusing on serum amylase as a potential measure of drug activity.
- The maximum tolerated dose (MTD) was set at 100 mg, as participants at 115 mg experienced significant adverse effects, including one case of severe hypersalivation.
- Although the overall amylase results were not significant, there was a notable trend showing that salivary amylase levels might indicate M3 activity at the higher dose.
$100 - $150
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Determination of xanomeline (LY246708 tartrate), an investigational agent for the treatment of Alzheimer's disease, in rat and monkey plasma by capillary gas chromatography with nitrogen-phosphorus detection.
London, UK
2 hours ago
1 Received
- A gas chromatography (GC) method was developed to measure xanomeline and its metabolites in rat and monkey plasma using hexane extraction.
- * The analytes were separated using a specific capillary column and detected with nitrogen-phosphorus detection, achieving a quantitation limit of 8 ng/ml.
- * This method is relevant for research on xanomeline's potential as a treatment for Alzheimer's disease.
$100 - $150
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Determination of xanomeline and active metabolite, N-desmethylxanomeline, in human plasma by liquid chromatography-atmospheric pressure chemical ionization mass spectrometry.
London, UK
2 hours ago
1 Received
- A new method has been developed for measuring xanomeline and its active metabolite from plasma samples using hexane extraction.
- The process involves drying the hexane extract, reconstituting it, and analyzing it through advanced mass spectrometry.
- This validated method is highly sensitive, quick (under 3 minutes per sample), and reliable, with quantitation limits of 75 pg/ml for xanomeline and 200 pg/ml for its metabolite.
$100 - $150
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High-performance liquid chromatographic assay for xanomeline, a specific M-1 agonist, and its metabolite in human plasma.
London, UK
2 hours ago
1 Received
- A reversed-phase HPLC assay was developed to monitor the drug xanomeline and its metabolite desmethylxanomeline in human plasma samples.
- The extraction process involved using hexane at basic pH, followed by evaporation and reconstitution with a specific acidic methanol solution for analysis.
- The method demonstrated high precision and accuracy, with a limit of quantification at 1.5 ng/ml and a linear response range for clinical monitoring of drug concentrations.
$100 - $150
Hourly Rate
The safety and tolerance of xanomeline tartrate in patients with Alzheimer's disease.
London, UK
2 hours ago
1 Received
- Xanomeline tartrate is a drug that specifically targets the M1 receptor and has shown good tolerance at doses up to 50 mg in healthy elderly people.
- A study involving 48 Alzheimer's patients tested eight different doses of xanomeline tartrate over a week to find the maximum tolerated dose (MTD).
- The study found that the MTD for Alzheimer's patients was 100 mg taken three times a day, which is twice as high as the MTD established in healthy elderly volunteers.
$100 - $150
Hourly Rate
Functionally selective M1 muscarinic agonists. 3. Side chains and azacycles contributing to functional muscarinic selectivity among pyrazinylazacycles.
London, UK
2 hours ago
1 Received
- Researchers focused on enhancing the M1 agonist activity of compounds related to xanomeline by modifying the 3- and 6-positions of pyrazinylazacycles.
- A notable compound, [3-(hexyloxy)pyrazinyl]-quinuclidine 5i, demonstrated improved potency and efficacy compared to a previously studied compound (19), with (S)-5i being significantly more potent than (R)-5i.
- While 5i showed some functional selectivity for the M1 receptor, it was still less efficacious than xanomeline but better than another compound (5n) due to additional binding interactions from its unique side chain.
$100 - $150
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The muscarinic M1 agonist xanomeline increases soluble amyloid precursor protein release from Chinese hamster ovary-m1 cells.
London, UK
2 hours ago
1 Received
- The study compares the effects of xanomeline, a selective M1 agonist being tested for Alzheimer's treatment, with carbachol, a muscarinic agonist, on the secretion of soluble amyloid precursor protein (APPs) from human m1 receptor-transfected Chinese hamster ovary cells.
- Both xanomeline and carbachol significantly increased APPs release, but their effects were inhibited by atropine, indicating that their action is receptor-specific.
- The findings suggest that stimulating m1 muscarinic receptors with drugs like xanomeline could potentially aid in reducing amyloid plaque formation in Alzheimer's disease.
$100 - $150
Hourly Rate
M1 agonists for the treatment of Alzheimer's disease. Novel properties and clinical update.
London, UK
2 hours ago
1 Received
- The AF series compounds, particularly AF102B and AF150(S), are selective agonists for m1 muscarinic receptors, showing potential benefits for Alzheimer's disease treatment by enhancing secretions of amyloid precursor proteins and decreasing tau phosphorylation.
- These compounds act as partial or full agonists in different cellular contexts but function as antagonists in elevating cAMP levels compared to carbachol, showing a unique interaction with nerve growth factor (NGF) for neurite outgrowth.
- In clinical trials, AF102B demonstrated significant efficacy at higher doses in improving cognitive functions in Alzheimer's patients, indicating its potential for therapeutic use despite the limited clinical studies available on m1 agonists.
$100 - $150
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Scientific and ethical concerns in clinical trials in Alzheimer's patients: the bridging study.
London, UK
2 hours ago
1 Received
- This paper discusses the scientific and ethical challenges of conducting bridging studies for Alzheimer's disease (AD), which are crucial for determining the maximum tolerated dose (MTD) in patients before moving to phase II trials.
- It highlights that AD patients respond differently to cholinergic treatments compared to healthy individuals, making it essential to establish the appropriate MTD to maximize the chances of detecting treatment efficacy.
- Recommendations for successful bridging studies include using a fixed-dose panel design based on MTD from healthy volunteers, ensuring rigorous preclinical safety evaluations, and maintaining thorough oversight for patient safety and ethical considerations.
$100 - $150
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Advances in CNS Drugs. Recent advances and considerations in the treatment of schizophrenia.
London, UK
2 hours ago
1 Received
$100 - $150
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PET study of the M1-agonists [11C]xanomeline and [11C]butylthio-TZTP in monkey and man.
London, UK
2 hours ago
1 Received
- - Xanomeline is a new drug being tested for Alzheimer's disease that selectively targets M1 muscarinic receptors and has shown promise in clinical trials.
- - A study using PET imaging tracked the brain distribution of xanomeline and a related compound, revealing significant accumulation in areas like the neocortex and striatum.
- - The rapid penetration of these compounds into the human brain suggests that xanomeline could provide therapeutic effects with minimal side effects, making it a potentially safer option for treating Alzheimer's.
$100 - $150
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Alzheimer's disease: new pharmacological perspectives.
London, UK
2 hours ago
1 Received
$100 - $150
Hourly Rate
Effects of central muscarinic-1 receptor stimulation on blood pressure regulation.
London, UK
2 hours ago
1 Received
- Stimulation of M1 receptors in the central nervous system can increase blood pressure and heart rate, but this stimulation is reduced in Alzheimer's patients.
- A study was conducted on both Alzheimer's patients and healthy individuals after administering the M1 agonist xanomeline, revealing that xanomeline raised blood pressure and heart rate in healthy subjects but led to near-syncope events in both groups during head-up tilt.
- The findings suggest that xanomeline causes sympathetic stimulation when lying down but impairs blood pressure regulation when the body is tilted, highlighting potential risks in Alzheimer's patients who have lower M1 receptor activity.
$100 - $150
Hourly Rate
Effects of xanomeline, a selective muscarinic receptor agonist, on cognitive function and behavioral symptoms in Alzheimer disease.
London, UK
2 hours ago
1 Received
- - The study aimed to assess the effects of xanomeline tartrate, a selective muscarinic receptor agonist, on cognitive and behavioral symptoms in patients with Alzheimer's disease (AD) over a 6-month period.
- - A total of 343 patients aged 60 and older participated, receiving either xanomeline at varying doses or a placebo, with significant improvements noted in cognitive measures and reductions in behavioral symptoms for those on the high dose.
- - However, the high-dose group also experienced a higher rate of adverse events, particularly gastrointestinal issues, leading to a 52% discontinuation rate due to side effects, highlighting the need for cautious consideration of dosage.
$100 - $150
Hourly Rate