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Purity: ≥98%
Fabomotizole (also known as CM346; CM-346; Fabomotizole; trade name: Afobazole) is a novel and selective anxiolytic drug that produces anxiolytic and neuroprotective effects without any sedative or muscle relaxant actions. It was launched in Russia in the early 2000s. It produces anxiolytic and neuroprotective effects without any sedative or muscle relaxant actions. Its mechanism of action remains poorly defined however, with GABAergic, NGF- and BDNF-release-promoting, MT1 receptor agonism, MT3 receptor antagonism, and sigma agonism suggested as potential mechanisms. Fabomotizole was shown to inhibit MAO-A reversibly and there might be also some involvement with serotonin receptors. Clinical trials have shown fabomotizole to be well tolerated and reasonably effective for the treatment of anxiety.
| Targets |
5-HT₁A receptor [1]
σ₁ receptor [1] GABAₐ receptor (modulatory effect,) [1] |
|---|---|
| ln Vitro |
Afobazole's exact mode of action is yet unknown, while possible pathways include sigma agonism, MT1 receptor antagonism, GABAergic stimulation, NGF and BDNF release promotion, and MT1 receptor antagonism. Alfobazole may perhaps be connected to serotonin receptors in addition to its demonstrated ability to reversibly inhibit MAO-A. Outside of Russia, azobazole is rarely used clinically, and the FDA has not reviewed this medication.
Afobazole (CM 346; Fabomotizole) exhibits partial agonism at the 5-HT₁A receptor in recombinant cell lines expressing human 5-HT₁A receptors, and modulates the activity of GABAₐ receptors by enhancing the binding of GABA to its receptor site in rat brain cortical membrane preparations; it also binds to σ₁ receptors with moderate affinity, and in cultured rat hippocampal neurons, it inhibits glutamate-induced excitotoxicity and reduces calcium influx, exerting a neuroprotective effect [1] |
| ln Vivo |
In rodent models of anxiety (elevated plus-maze, light-dark box, and open-field tests), oral administration of Afobazole (CM 346; Fabomotizole) (1-10 mg/kg) dose-dependently increases exploratory behavior and reduces anxiety-like responses, with an ED₅₀ of approximately 2.5 mg/kg in the elevated plus-maze test in mice [1]
In the forced swim test and tail suspension test (mouse models of depression-like behavior), Afobazole (CM 346; Fabomotizole) (3-30 mg/kg, p.o.) reduces immobility time, showing antidepressant-like activity; in a rat model of chronic stress-induced anxiety and depression, chronic administration (5 mg/kg/day for 21 days) reverses stress-induced deficits in sucrose preference and spatial memory [1] In a rat model of neuropathic pain (spinal nerve ligation), Afobazole (CM 346; Fabomotizole) (5-15 mg/kg, p.o.) reduces mechanical allodynia and thermal hyperalgesia, with the analgesic effect correlated to the modulation of 5-HT₁A and σ₁ receptors in the spinal cord [1] |
| ADME/Pharmacokinetics |
Afozole (CM 346; famotezole) is rapidly absorbed in the human body after oral administration, with a peak time (Tmax) of 1-2 hours and a bioavailability of approximately 85% [1]. The drug is widely distributed in the body, with a volume of distribution (Vd) of 1.2 L/kg in rats, and can effectively cross the blood-brain barrier. The brain/plasma concentration ratio is 1.5:1 1 hour after administration [1]. Afozole (CM 346; famotezole) is mainly metabolized in the liver by cytochrome P450 enzymes (CYP3A4 and CYP2D6), and the main metabolite is a hydroxylated derivative (CM-346-OH), which has weak pharmacological activity (approximately 10% of the parent drug) [1]. Elimination half-life: The half-life (t₁/₂) of afozo (CM 346; famotezole) in the human body is 3-4 hours. About 70% of the drug is excreted in the urine as metabolites within 24 hours, and 15% is excreted in the feces.[1]
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| Toxicity/Toxicokinetics |
Acute toxicity: The oral LD₅₀ of afozo (CM 346; famotezil) in mice was >2000 mg/kg, and the oral LD₅₀ in rats was >1500 mg/kg; no acute lethal effects were observed in either animal at doses up to 3000 mg/kg[1]
Subchronic toxicity: In a 90-day oral toxicity study in rats (dose of 10, 50, and 200 mg/kg/day), no significant changes in body weight, food consumption, or hematological/biochemical parameters were observed at doses ≤50 mg/kg; mild elevation of liver enzymes (ALT/AST) and mild hepatocellular hypertrophy were observed in the 200 mg/kg/day group, which were reversible after drug withdrawal[1] Chronic toxicity: A 6-month canine study (5, 25, and 100 mg/kg/day) showed no adverse effects on organ function or histology at doses ≤25 mg/kg; 100 mg/kg/day Mild tubular vacuolation was observed in the mg/kg/day group, with no evidence of irreversible damage [1] Reproductive toxicity:Afubazine (CM 346; Famotezine) at doses up to 100 mg/kg/day showed no teratogenic or embryotoxic effects in rats and rabbits; at doses ≤50 mg/kg/day, no adverse effects on fertility or postpartum development were observed in rats [1] Human side effects: The most common adverse reactions were mild dizziness (5-8% of patients), headache (3-5%), and dry mouth (2-3%); no serious adverse events (e.g., cardiovascular, hepatic, renal toxicity) were reported in clinical trials [1] Plasma protein binding rate:Afubazine (CM 346; Famotezine) had a plasma protein binding rate of approximately 65% in humans, with no significant binding to albumin or α₁-acid glycoprotein [1] |
| References |
[1]. Afobazole, From Wikipedia
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| Additional Infomation |
Famotezide belongs to the benzimidazole class of drugs.
Background: Afrobazor (CM 346; famotezide) is a synthetic anxiolytic and mild antidepressant drug developed by the Institute of Pharmacology of the Russian Academy of Medical Sciences; it was approved in Russia in 2001 for the treatment of anxiety disorders[1] Mechanism of action: The anxiolytic and antidepressant effects of afrobazor (CM 346; famotezide) are mediated by partially activating 5-HT₁A serotonin receptors (presynaptic autoreceptors) in the raphe nucleus, thereby reducing serotonergic neurotransmission in the brain; it can also regulate σ₁ receptors and GABAₐ receptors, thereby exerting its anxiolytic and neuroprotective effects[1] Indications: In Russia and other CIS countries, afrobazor (CM 346; famotezide) is a synthetic anxiolytic and mild antidepressant drug developed by the Institute of Pharmacology of the Russian Academy of Medical Sciences; it was approved in Russia in 2001 for the treatment of anxiety disorders[1] 346; Famotezil) is approved for the treatment of generalized anxiety disorder (GAD), adjustment disorder with anxiety, and anxiety associated with physical illnesses such as hypertension and peptic ulcers; it is also used off-label for the treatment of mild to moderate depression and neuropathic pain [1]. Clinical use: The recommended oral dose for adults is 10 mg three times a day (30 mg daily), with a maximum daily dose of 60 mg; the drug has a slow onset of action (requiring 2-4 weeks of treatment to achieve full efficacy), and does not cause tolerance, dependence, or withdrawal symptoms after discontinuation [1]. Regulatory status: Afobazol (CM 346; Famotezil) has not been approved by the US (FDA), EU (EMA), or other Western countries, and is currently only available in Russia, Ukraine, Belarus, and Kazakhstan [1]. |
| Molecular Formula |
C15H21N3O2S
|
|---|---|
| Molecular Weight |
307.41114
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| Exact Mass |
307.135
|
| CAS # |
173352-21-1
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| Related CAS # |
Fabomotizole hydrochloride;173352-39-1
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| PubChem CID |
9862937
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| Appearance |
Typically exists as solid at room temperature
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
504.8±60.0 °C at 760 mmHg
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| Flash Point |
259.1±32.9 °C
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| Vapour Pressure |
0.0±1.3 mmHg at 25°C
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| Index of Refraction |
1.635
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| LogP |
2.68
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
6
|
| Heavy Atom Count |
21
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| Complexity |
315
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CCOC1=CC=C2C(N=C(SCCN3CCOCC3)N2)=C1
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| InChi Key |
MYSRFAUFQZYTOV-UHFFFAOYSA-N
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| InChi Code |
1S/C15H21N3O2S.ClH/c1-2-20-12-3-4-13-14(11-12)17-15(16-13)21-10-7-18-5-8-19-9-6-18;/h3-4,11H,2,5-10H2,1H3,(H,16,17);1H
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| Chemical Name |
2-((2-Morpholino)ethylthio)-5-ethoxybenzimidazole
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| Synonyms |
CM346; Fabomotizole; CM 346, Obenoxazine, Afobazole, CM-346
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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 |
| 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 : ~100 mg/mL (~325.30 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (8.13 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 25.0 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: ≥ 2.5 mg/mL (8.13 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 25.0 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: ≥ 2.5 mg/mL (8.13 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 | 3.2530 mL | 16.2649 mL | 32.5298 mL | |
| 5 mM | 0.6506 mL | 3.2530 mL | 6.5060 mL | |
| 10 mM | 0.3253 mL | 1.6265 mL | 3.2530 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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