| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg | |||
| Other Sizes |
| Targets |
Rilmazafone hydrochloride acts as a selective ligand for the GABA receptor, specifically targeting the benzodiazepine (omega) binding site on the GABAA receptor complex. It is a prodrug that itself does not bind to benzodiazepine receptors but is metabolized to active benzodiazepine metabolites that act as positive allosteric modulators at the GABA-A receptor benzodiazepine site. The compound also inhibits the enzyme peptidyl-prolyl cis-trans isomerase A (PPIA). Its primary pathway is Membrane Transporter/Ion Channel and Neuronal Signaling via the GABA receptor.
|
|---|---|
| ln Vitro |
In vitro studies have demonstrated that rilmazafone hydrochloride functions as a potent inhibitor of the enzyme peptidyl-prolyl cis-trans isomerase A (PPIA), binding to PPIA and preventing the formation of peptidyl-prolyl bonds in proteins. As a benzodiazepine prodrug, its in vitro activity is characterized by its conversion to active metabolites that exhibit anxiolytic and sedative effects. The compound has been shown to stimulate hepatic drug-metabolizing enzymes in various species, accompanied by a marked reduction in the pharmacological activity of pentobarbital in rats.
|
| ln Vivo |
In order to stimulate hepatic drug-metabolizing enzymes in rats that have received high doses of limazafone hydrochloride (450191-S; 200 or 600 mg/kg for 5 or 3 days, respectively), oral dosages of limazafone metabolites Based on the increased enzyme activity, there was a considerable reduction in the plasma concentration of 200 mg/kg Rilmazafone. Rats pretreated with phenobarbital also showed a reduction in plasma metabolite levels, which was nearly the same as the reduction observed with limazafone pretreatment. However, when rats were given β-naphthoflavone, their plasma levels of the metabolite were higher and their clearance was slower than when rats were given limazadone or phenobarbital as a pretreatment. In rats, mice, and dogs, rimazafone has been demonstrated to increase hepatic drug-metabolizing enzymes while dramatically lowering pentobarbital's pharmacological action. Rimazafone induces liver enzyme activity, however this effect is only noticeable when the metabolites' plasma concentrations are extremely high [2].
In vivo, rilmazafone hydrochloride functions as a sleep inducer with sedative and hypnotic properties. In animal studies, administration of rilmazafone to rats, mice, and dogs resulted in stimulation of hepatic drug-metabolizing enzymes, accompanied by a significant reduction in the pharmacological activity of pentobarbital. In patients with chronic renal failure, the pharmacokinetics are significantly altered, with metabolite Cmax doubling and AUC increasing five-fold compared to healthy volunteers. The active metabolite M1 and M4 show altered exposure in renally impaired patients. |
| Enzyme Assay |
The in vitro enzyme/receptor binding assay for rilmazafone hydrochloride typically involves radioligand binding studies using membrane preparations from brain tissue expressing GABAA receptors. Competitive binding assays are performed with varying concentrations of the test compound and a radiolabeled benzodiazepine ligand to determine affinity for the benzodiazepine binding site. For PPIA inhibition, enzymatic assays measure the inhibition of peptidyl-prolyl cis-trans isomerase activity using a suitable peptide substrate, with IC50 values determined from dose-response curves. Data analysis using nonlinear regression models yields binding affinities (Ki or IC50) and confirms the compound's interaction with the target.
|
| Cell Assay |
In vitro cellular assays for rilmazafone hydrochloride are conducted using cultured neuronal cell lines expressing GABAA receptors. Cells are plated in multi-well plates and treated with varying concentrations of rilmazafone or its active metabolites. Functional activity is assessed by measuring chloride influx using fluorescent indicators or patch-clamp electrophysiology to record GABAA receptor-mediated currents. Cell viability and cytotoxicity are evaluated using standard assays such as MTT or LDH release. For PPIA-related studies, protein interaction assays are performed in cell lysates. Data are collected from multiple replicates and analyzed to determine EC50 or IC50 values.
|
| Animal Protocol |
In vivo animal studies for rilmazafone hydrochloride are typically performed in rodents (rats and mice) and dogs. The compound is administered orally or via intraperitoneal injection at various doses. Pharmacodynamic effects are assessed by measuring sleep induction, pentobarbital-induced sleep time prolongation, and motor function impairment. Blood and tissue samples are collected at predetermined time points for pharmacokinetic analysis of the prodrug and its active metabolites. Hepatic enzyme induction is evaluated by measuring drug-metabolizing enzyme activities in liver homogenates. Behavioral tests such as open field and rotarod are used to assess sedative and motor effects.
|
| ADME/Pharmacokinetics |
Rilmazafone hydrochloride is an orally active prodrug that is exclusively metabolized to its desglycylated metabolite (DG) and cyclic active form (M1) by aminopeptidases in the small intestine. The elimination half-life is approximately 10.5 hours, and the drug is excreted primarily via urine. In patients with renal impairment, the pharmacokinetic profile is significantly altered: Cmax of metabolites doubles and AUC increases five-fold compared to healthy volunteers. The compound is distributed throughout the central nervous system via passive diffusion and active transport mechanisms.
|
| Toxicity/Toxicokinetics |
In toxicology studies, rilmazafone hydrochloride has been shown to induce hepatic drug-metabolizing enzymes in rats, mice, and dogs at high doses, which is accompanied by a marked reduction in the pharmacological activity of pentobarbital. The compound induces impairment of motor function as part of its sedative-hypnotic profile. Long-term safety data indicate that the compound has a distinct liability profile compared to renally-cleared hypnotics such as zolpidem. Standard toxicological assessments including acute, subchronic, and chronic toxicity studies have been conducted to establish the safety profile for clinical use.
|
| References |
|
| Additional Infomation |
Rilmazafone hydrochloride (450191-S) is a water-soluble benzodiazepine prodrug developed in Japan and marketed under the name Rhythmy. It has sedative and hypnotic effects and is used clinically as a sleep inducer. The compound is a ring-opened derivative of benzodiazepines. Clinical studies have been conducted in patients with chronic renal failure to determine appropriate dosing. The active metabolite formed in vivo is 8-chloro-6-(2-chlorophenyl)-N,N-dimethyl-4H-1,2,4-triazolo benzodiazepine-2-carboxamide. The compound is not approved in many countries but remains a research tool.
|
| Molecular Formula |
C21H20N6O3CL2.HCL
|
|---|---|
| Molecular Weight |
511.78884
|
| Exact Mass |
510.074
|
| CAS # |
85815-37-8
|
| Related CAS # |
Rilmazafone;99593-25-6
|
| PubChem CID |
9958041
|
| Appearance |
White to off-white solid powder
|
| LogP |
4.424
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
6
|
| Rotatable Bond Count |
7
|
| Heavy Atom Count |
33
|
| Complexity |
696
|
| Defined Atom Stereocenter Count |
0
|
| InChi Key |
KHINGHZNENOVFD-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C21H20Cl2N6O3.ClH/c1-28(2)21(32)20-26-17(11-25-18(30)10-24)29(27-20)16-8-7-12(22)9-14(16)19(31)13-5-3-4-6-15(13)23;/h3-9H,10-11,24H2,1-2H3,(H,25,30);1H
|
| Chemical Name |
5-[[(2-aminoacetyl)amino]methyl]-1-[4-chloro-2-(2-chlorobenzoyl)phenyl]-N,N-dimethyl-1,2,4-triazole-3-carboxamide;hydrochloride
|
| 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 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)
|
| Solubility (In Vitro) |
DMSO : ~250 mg/mL (~488.48 mM)
|
|---|---|
| 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 | 1.9539 mL | 9.7696 mL | 19.5393 mL | |
| 5 mM | 0.3908 mL | 1.9539 mL | 3.9079 mL | |
| 10 mM | 0.1954 mL | 0.9770 mL | 1.9539 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
