| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
The primary molecular target is the muscarinic acetylcholine receptor. Metixene competitively antagonizes acetylcholine at muscarinic receptors in the corpus striatum, restoring the balance between dopamine and acetylcholine. It also shows antihistaminic activity and direct antispasmodic effects on smooth muscle. It potently inhibits QNB binding to rat striatal membranes.
|
|---|---|
| ln Vitro |
Metixene, with IC50 and Ki values of 55 nM and 15 nM, respectively, has the ability to inhibit QNB's binding to muscarinic receptors [3].
In vitro, metixene inhibits tritiated quinuclidinyl benzilate binding to rat striatal membranes with nanomolar affinity. It antagonizes carbachol-induced contractions in isolated guinea pig ileum and inhibits histamine-induced contractions in smooth muscle preparations. |
| ln Vivo |
In vivo, metixene reduces tremor induced by tremorine or oxotremorine in mice and rats. It also improves motor function in animal models of parkinsonism, such as reserpine-induced akinesia, and shows antispasmodic activity in gastrointestinal smooth muscle models.
|
| Enzyme Assay |
Radioligand binding assays use tritiated quinuclidinyl benzilate to label muscarinic receptors in rat brain striatal membranes. Competition binding curves are generated with increasing concentrations of metixene, and Ki values are determined by non-linear regression to assess affinity for M1 and M2 subtypes.
|
| Cell Assay |
Isolated guinea pig ileum or tracheal smooth muscle preparations are mounted in organ baths. Tissues are contracted with carbachol or histamine, and metixene is added cumulatively. Relaxation responses are recorded isometrically to calculate IC50 values and assess competitive antagonism.
|
| Animal Protocol |
Mice or rats receive metixene by intraperitoneal or oral administration. Tremor is induced by tremorine or oxotremorine, and tremor severity is scored. Reserpine-induced akinesia is assessed by locomotor activity monitoring. Antispasmodic activity is evaluated in gastrointestinal motility models.
|
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion
Absorbed via the gastrointestinal tract after oral administration, but the extent of absorption is unclear. Metabolism/Metabolites Metabolized in the liver. Primarily through sulfoxide formation and N-demethylation. |
| Toxicity/Toxicokinetics |
Toxicity Summary
Parkinson's disease is believed to be caused by an imbalance between the excitatory (cholinergic) and inhibitory (dopaminergic) systems in the striatum. The mechanism of action of centrally active anticholinergic drugs (such as methecin) is thought to involve competitive antagonism of acetylcholine on striatal muscarinic receptors, thereby restoring this balance. |
| References |
[1]. Syvälahti EK, et al. Effects of antiparkinsonian drugs on muscarinic receptor binding in rat brain, heart and lung. Pharmacol Toxicol. 1988 Feb;62(2):90-4.
[2]. J. Hagenah, et al. Exogenous levodopa is not toxic to elderly subjects with non-parkinsonian movement disorders: further clinical evidence. , 106(3-4), 301–307. doi:10.1007/s007020050159 [3]. S L Levin, et al. Dualism in the effect of cholinolytics upon the human parotid gland deprived of parasympathetic control. Int J Clin Pharmacol Res. 1986;6(5):429-39. |
| Additional Infomation |
Metixene belongs to the thiol and piperidine class of compounds. It is an anti-Parkinson's disease drug, and also a muscarinic receptor antagonist and histamine receptor antagonist. Metixene (or methiothiazide) is an anticholinergic drug used as an anti-Parkinson's disease medication. Metixene is only present in individuals who have used or taken this drug. It is an anticholinergic drug used as an anti-Parkinson's disease medication. Drug Indications For the treatment of symptoms of Parkinson's disease. Mechanism of Action Parkinson's disease is thought to be caused by an imbalance between the excitatory (cholinergic) and inhibitory (dopaminergic) systems in the striatum. The mechanism of action of centrally active anticholinergic drugs (such as Metixene) is thought to involve competitive antagonism of acetylcholine on muscarinic receptors in the striatum, thereby restoring balance.
Pharmacodynamics Methecin is a tertiary amine antimuscarinic drug with effects similar to atropine; it also has antihistamine and direct-acting antispasmodic effects. It was used to treat Parkinson's disease symptoms, including relieving extrapyramidal symptoms caused by other drugs such as phenothiazines, but like other antimuscarinic drugs, it is ineffective for tardive dyskinesia. Methecin is discontinued. |
| Molecular Formula |
C20H23NS
|
|---|---|
| Molecular Weight |
309.46832
|
| Exact Mass |
309.155
|
| CAS # |
4969-02-2
|
| Related CAS # |
Metixene hydrochloride hydrate;7081-40-5;Metixene hydrochloride;1553-34-0
|
| PubChem CID |
4167
|
| Appearance |
Typically exists as solid at room temperature
|
| Boiling Point |
bp0.07 171-175°
|
| Melting Point |
< 25 °C
< 25 °C |
| LogP |
4.952
|
| Hydrogen Bond Donor Count |
0
|
| Hydrogen Bond Acceptor Count |
2
|
| Rotatable Bond Count |
2
|
| Heavy Atom Count |
22
|
| Complexity |
349
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
CN1CCCC(CC2C3=CC=CC=C3SC3=CC=CC=C23)C1
|
| InChi Key |
MJFJKKXQDNNUJF-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C20H23NS/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
|
| Chemical Name |
1-methyl-3-(9H-thioxanthen-9-ylmethyl)piperidine
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
|
|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
