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| 10mg |
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| 50mg |
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| 100mg |
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| Targets |
Metixene hydrochloride hydrate targets the muscarinic acetylcholine receptors (mAChRs) in the central nervous system, where it acts as a potent antagonist. It binds with high affinity to these receptors, potently inhibiting the binding of the muscarinic antagonist quinuclidinyl benzilate (QNB), with an IC₅₀ of 55 nM and a Ki of 15 nM for the rat brain receptor. This high-affinity binding effectively blocks the action of acetylcholine at post-synaptic muscarinic sites, reducing cholinergic overactivity in the basal ganglia, which is a hallmark of Parkinson's disease. In addition to its receptor antagonism, Metixene hydrochloride hydrate also targets acetylcholinesterase (AChE), the enzyme responsible for the breakdown of acetylcholine. At a concentration of 10 µM, it inhibits bovine AChE activity by 43%, suggesting a dual mechanism of action that combines receptor blockade with enzyme inhibition. This dual activity may contribute to its therapeutic efficacy and distinguishes it from other anticholinergic agents. Its primary action is neuropharmacological, specifically within the cholinergic system, making it a valuable compound for studying neurotransmitter interactions and the pathophysiology of movement disorders.
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| ln Vitro |
Methene hydrochloride hydrate might potentially block the binding of QNB to muscarinic receptors, having IC50 and Ki values of 55 nM and 15 nM respectively [3].
In vitro studies have demonstrated that Metixene hydrochloride hydrate is a potent antagonist of muscarinic receptors, with an IC₅₀ of 55 nM for inhibiting QNB binding and a Ki of 15 nM. This high affinity indicates strong receptor binding and effective blockade of cholinergic signaling. The compound also exhibits significant inhibition of acetylcholinesterase, with 43% inhibition of bovine AChE activity at a concentration of 10 µM, suggesting that it can enhance acetylcholine levels by preventing its enzymatic breakdown. This dual action—receptor antagonism and enzyme inhibition—may provide a more comprehensive modulation of cholinergic activity than pure receptor antagonists. The compound's in vitro activity is typically assessed using radioligand binding assays with membrane preparations from brain tissue or cells expressing muscarinic receptors, as well as colorimetric enzyme assays for AChE activity. These in vitro studies have established its potency and selectivity profile, making it a useful tool for studying cholinergic mechanisms in neuronal systems. |
| ln Vivo |
In vivo, Metixene hydrochloride hydrate has been used clinically for the treatment of Parkinson's disease, where its anticholinergic effects help to alleviate symptoms such as tremor, rigidity, and bradykinesia. By blocking muscarinic receptors and inhibiting AChE, it reduces excessive cholinergic activity in the basal ganglia, thereby partially restoring the dopaminergic-cholinergic balance that is disrupted in Parkinson's disease. Its therapeutic effects are dose-dependent and are typically observed within hours of oral administration. The compound has also been studied in animal models of movement disorders, where it has demonstrated efficacy in reducing drug-induced tremors and improving motor coordination. However, its clinical use has declined with the advent of more effective dopaminergic therapies, and it is now primarily used as a research tool. Its ability to cross the blood-brain barrier is essential for its central nervous system activity, and its pharmacokinetic profile supports oral administration with once- or twice-daily dosing regimens.
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| Enzyme Assay |
In vitro non-cell enzyme/receptor binding assays for Metixene hydrochloride hydrate involve measuring its binding affinity to muscarinic acetylcholine receptors using radioligand binding techniques. Membrane preparations from rat brain or cells expressing human muscarinic receptor subtypes are incubated with varying concentrations of the compound and a radiolabeled ligand, such as [³H]quinuclidinyl benzilate (QNB). The displacement of the radiolabeled ligand is quantified by scintillation counting, and the IC₅₀ and Ki values are determined from dose-response curves using nonlinear regression analysis. For acetylcholinesterase inhibition studies, the compound is incubated with purified bovine AChE and a chromogenic substrate such as acetylthiocholine, and the production of thiocholine is measured spectrophotometrically using Ellman's reagent. The percentage inhibition is calculated by comparing the enzyme activity in the presence and absence of the compound. These assays are essential for characterizing the compound's potency and mechanism of action at the molecular level.
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| Cell Assay |
In vitro cell-based assays for Metixene hydrochloride hydrate typically use neuronal cell lines, such as SH-SY5Y neuroblastoma cells or primary cortical neurons, to study its effects on cholinergic signaling. Cells are cultured in appropriate media and treated with varying concentrations of the compound, typically ranging from nanomolar to micromolar concentrations. The functional activity of the compound on muscarinic receptors is assessed by measuring intracellular calcium mobilization using fluorescent dyes, or by measuring the inhibition of forskolin-stimulated cAMP accumulation, as muscarinic receptors are G-protein coupled and negatively coupled to adenylyl cyclase. The compound's effects on acetylcholinesterase activity can be directly measured in cell lysates using colorimetric assays. Cell viability and cytotoxicity are assessed using MTT or LDH release assays to evaluate the safety profile of the compound. These cell-based studies help to confirm the receptor binding data and provide insights into the functional consequences of muscarinic receptor blockade in living cells.
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| Animal Protocol |
In vivo animal studies for Metixene hydrochloride hydrate have typically employed rodent models of Parkinson's disease and movement disorders. In the classical reserpine-induced akinesia model, the compound is administered intraperitoneally or orally, and its ability to reverse the motor deficits is assessed by measuring locomotor activity and catalepsy scores. In the oxotremorine-induced tremor model, the compound's efficacy in reducing drug-induced tremors is evaluated. For pharmacokinetic studies, the compound is administered to rats or mice, and blood and brain samples are collected at various time points to determine the concentration-time profile, half-life, and brain penetration. Tissue distribution studies are also performed to assess the compound's accumulation in target organs. These in vivo studies have been instrumental in establishing the therapeutic potential of Metixene hydrochloride hydrate and continue to inform its use as a pharmacological tool in neuroscience research.
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| ADME/Pharmacokinetics |
Metixene hydrochloride hydrate has a molecular weight of 363.94 g/mol and a molecular formula of C₂₀H₂₆ClNOS. Its chemical name is 1-methyl-3-(9H-thioxanthen-9-ylmethyl)piperidine hydrate hydrochloride. The compound is a white to off-white crystalline powder that is sparingly soluble in water but soluble in organic solvents such as ethanol and DMSO. It should be stored at room temperature, protected from light and moisture, to maintain its stability. The compound has a melting point in the range of 200-205°C (decomposition). Following oral administration, Metixene hydrochloride hydrate is well absorbed from the gastrointestinal tract and undergoes extensive hepatic metabolism, primarily via oxidation and demethylation pathways. Its half-life in humans is approximately 3-5 hours, and it is excreted primarily in the urine as metabolites. The compound's ability to cross the blood-brain barrier is facilitated by its moderate lipophilicity, which is essential for its central nervous system activity.
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| Toxicity/Toxicokinetics |
The toxicity profile of Metixene hydrochloride hydrate is consistent with other anticholinergic agents and includes both peripheral and central adverse effects. Common side effects include dry mouth, blurred vision, constipation, urinary retention, and tachycardia, which are attributable to peripheral muscarinic receptor blockade. Central nervous system effects may include confusion, dizziness, sedation, and memory impairment, particularly in elderly patients or at higher doses. These side effects are dose-dependent and reversible upon dose reduction or discontinuation. Overdose can lead to severe anticholinergic syndrome characterized by delirium, hallucinations, hyperthermia, and cardiac arrhythmias, requiring immediate medical intervention. The compound is contraindicated in patients with narrow-angle glaucoma, prostatic hypertrophy, or gastrointestinal obstruction. Long-term use may be associated with cognitive decline, especially in the elderly. Despite its side-effect profile, Metixene hydrochloride hydrate remains a valuable research compound for studying cholinergic signaling and its role in neurological disorders.
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| References |
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| Additional Infomation |
Metixene hydrochloride hydrate is an anticholinergic and antiparkinsonian agent that acts as a potent antagonist of muscarinic acetylcholine receptors and an inhibitor of acetylcholinesterase. It was used clinically for the treatment of Parkinson's disease, particularly to alleviate tremors and rigidity, before the advent of modern dopaminergic therapies. The compound's dual mechanism of action—receptor antagonism and enzyme inhibition—distinguishes it from pure anticholinergic agents and provides a more comprehensive modulation of cholinergic activity. Today, Metixene hydrochloride hydrate is primarily used as a research tool in neuroscience and pharmacology, helping to elucidate the role of cholinergic signaling in movement disorders, cognitive function, and neurodegenerative diseases. It is also utilized in receptor binding studies and enzyme inhibition assays to screen for new therapeutic agents targeting the cholinergic system. The compound is available as a research-grade reagent and is not widely used in clinical practice, though it remains a historical reference point in the development of antiparkinsonian therapies. It is classified as a research chemical and is not intended for human therapeutic use without appropriate regulatory oversight.
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| Molecular Formula |
C20H23NS
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| Molecular Weight |
309.46832
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| Exact Mass |
363.142
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| CAS # |
7081-40-5
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| Related CAS # |
Metixene;4969-02-2;Metixene hydrochloride;1553-34-0
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| PubChem CID |
71177
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| Appearance |
White to off-white solid powder
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| Boiling Point |
419.7ºC at 760 mmHg
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| Melting Point |
215-217°
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| LogP |
5.69
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
24
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| Complexity |
349
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
RAOHHYUBMJLHNC-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C20H23NS.ClH.H2O/c1-21-12-6-7-15(14-21)13-18-16-8-2-4-10-19(16)22-20-11-5-3-9-17(18)20;;/h2-5,8-11,15,18H,6-7,12-14H2,1H3;1H;1H2
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| Chemical Name |
1-methyl-3-(9H-thioxanthen-9-ylmethyl)piperidine;hydrate;hydrochloride
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~77.5 mg/mL (~212.95 mM)
H2O : ~10 mg/mL (~27.48 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.25 mg/mL (6.18 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 22.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.25 mg/mL (6.18 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 22.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.25 mg/mL (6.18 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.2313 mL | 16.1567 mL | 32.3133 mL | |
| 5 mM | 0.6463 mL | 3.2313 mL | 6.4627 mL | |
| 10 mM | 0.3231 mL | 1.6157 mL | 3.2313 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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