WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H319793
CAS#: 173352-39-1 (HCl)
Description: Fabomotizole, also known as Afobazole, Obenoxazine and CM346, is an anxiolytic drug 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.
Hodoodo Cat#: H319793
Name: Fabomotizole HCl
CAS#: 173352-39-1 (HCl)
Chemical Formula: C15H22ClN3O2S
Exact Mass: 307.14
Molecular Weight: 343.870
Elemental Analysis: C, 52.39; H, 6.45; Cl, 10.31; N, 12.22; O, 9.31; S, 9.32
Related CAS #: 173352-21-1 (free base) 173352-39-1 (HCl) 189638-30-0 (2HCl) Fabomotizole mesylate
Synonym: CM-346; CM346; CM 346; Fabomotizole; Obenoxazine; Afobazol; Afobazole; Aphobazole; Afobazole HCl; Afobazole hydrochloride
IUPAC/Chemical Name: 4-(2-((5-ethoxy-1H-benzo[d]imidazol-2-yl)thio)ethyl)morpholine hydrochloride
InChi Key: MYSRFAUFQZYTOV-UHFFFAOYSA-N
InChi Code: InChI=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
SMILES Code: CCOC1=CC=C2NC(SCCN3CCOCC3)=NC2=C1.[H]Cl
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
More Info:
| Biological target: | Fabomotizole hydrochloride (CM346 hydrochloride) is an anxiolytic drug that produces anxiolytic and neuroprotective effects without any sedative or muscle relaxant actions. |
| In vitro activity: | Experiments were carried out to determine how afobazole affects neuronal and microglial responses to prolonged in vitro ischemia in rat cortical cells. Treatment with afobazole showed a decrease in microglial activation as reflected in the degree of membrane ruffling in response to ATP (Supplementary Figure S1). Application of afobazole (Afob) significantly mitigated microglial cell death by 75 ± 8% when co-incubated with ischemia (Figure 1Aiv,B). Therefore, it was examined how afobazole effects the levels of the death protease, caspase-3, in microglia after ischemia treatment. There was a notable increase in the number of microglia expressing caspase-3 following ischemia (Figure 3Ai,ii) and this upregulation was reduced by afobazole treatment (Figure 3Aiii,iv). Quantification of the images showed that afobazole alone significantly decreased caspase-3 expressing cells by 20 ± 3% relative to the control and diminished the increases in caspase-3 evoked by ischemia by 56 ± 5% (Figure 3B). This study demonstrates that afobazole can reduce microglial toxicity and cell death following prolonged ischemic exposure. These properties make afobazole an attractive drug for treatment of ischemic stroke. Reference: Front Neurosci. 2019; 13: 414. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6529844/ |
| In vivo activity: | To specifically test the hypothesis that fabomotizole could function in a Sigma1R agonist-like manner and provide anxiolytic effects, in vivo experiments were used. Dependence of anxiolytic properties of fabomotizole on Sigma1R was examined in the elevated plusmaze with male BALB/c mice in the presence of known Sigma1R antagonists. Fabomotizole administered at a 2.5 mg/kg dose 30 min prior to EPM exposition (Veh1 + Fab 2.5) led to a significantly higher number of entries into open arms and time spent in the open arms (adj p < 0.001) (Figure 1 and Figure 2, Table S1). Administration of BD-1047 (BD-1047 1.0 + Fab 2.5; adj p < 0.001) or NE-100 (NE-100 1.0 + Fab 2.5; adj p < 0.01) at a 1.0 mg/kg dose 30 min prior to fabomotizole prevented its effect and enhanced the anxietylike behavior, reducing entries into open arms (Figure 1 and Figure 2, Table S1). Fabomotizole (Veh1 + Fab 2.5) moderately raised the number of total entries (adj p = 0.045) (Figure S1, Table S2). Under administration of Sigma1R antagonist BD-1047 (BD-1047 1.0 + Fab 2.5) 30 min prior to fabomotizole, a statistically significant decrease in the number of closed arms entries and the number of total entries occurred (Figure S1, Table S2). Achieved results demonstrate the anxiolytic-like effect of fabomotizole and its elimination by the Sigma1R antagonists BD-1047 (1 mg/kg i.p.) and NE-100 (1 mg/kg i.p.). Reference: Int J Mol Sci. 2021 Jun; 22(11): 5455. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8196847/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 50.0 | 145.40 | |
| Ethanol | 50.0 | 145.40 |
The following data is based on the product molecular weight 343.87 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1 Behensky AA, Katnik C, Yin H, Cuevas J. Activation of Sigma Receptors With Afobazole Modulates Microglial, but Not Neuronal, Apoptotic Gene Expression in Response to Long-Term Ischemia Exposure. Front Neurosci. 2019 May 15;13:414. doi: 10.3389/fnins.2019.00414. PMID: 31156357; PMCID: PMC6529844. 2. Voronin MV, Kadnikov IA. Contribution of Sigma-1 receptor to cytoprotective effect of afobazole. Pharmacol Res Perspect. 2016 Nov 7;4(6):e00273. doi: 10.1002/prp2.273. PMID: 28097006; PMCID: PMC5226281. 3. Voronin MV, Vakhitova YV, Tsypysheva IP, Tsypyshev DO, Rybina IV, Kurbanov RD, Abramova EV, Seredenin SB. Involvement of Chaperone Sigma1R in the Anxiolytic Effect of Fabomotizole. Int J Mol Sci. 2021 May 21;22(11):5455. doi: 10.3390/ijms22115455. PMID: 34064275; PMCID: PMC8196847. 4. Kadnikov IA, Verbovaya ER, Voronkov DN, Voronin MV, Seredenin SB. Deferred Administration of Afobazole Induces Sigma1R-Dependent Restoration of Striatal Dopamine Content in a Mouse Model of Parkinson's Disease. Int J Mol Sci. 2020 Oct 15;21(20):7620. doi: 10.3390/ijms21207620. PMID: 33076300; PMCID: PMC7593947. |
| In vitro protocol: | 1 Behensky AA, Katnik C, Yin H, Cuevas J. Activation of Sigma Receptors With Afobazole Modulates Microglial, but Not Neuronal, Apoptotic Gene Expression in Response to Long-Term Ischemia Exposure. Front Neurosci. 2019 May 15;13:414. doi: 10.3389/fnins.2019.00414. PMID: 31156357; PMCID: PMC6529844. 2. Voronin MV, Kadnikov IA. Contribution of Sigma-1 receptor to cytoprotective effect of afobazole. Pharmacol Res Perspect. 2016 Nov 7;4(6):e00273. doi: 10.1002/prp2.273. PMID: 28097006; PMCID: PMC5226281. |
| In vivo protocol: | 1. Voronin MV, Vakhitova YV, Tsypysheva IP, Tsypyshev DO, Rybina IV, Kurbanov RD, Abramova EV, Seredenin SB. Involvement of Chaperone Sigma1R in the Anxiolytic Effect of Fabomotizole. Int J Mol Sci. 2021 May 21;22(11):5455. doi: 10.3390/ijms22115455. PMID: 34064275; PMCID: PMC8196847. 2. Kadnikov IA, Verbovaya ER, Voronkov DN, Voronin MV, Seredenin SB. Deferred Administration of Afobazole Induces Sigma1R-Dependent Restoration of Striatal Dopamine Content in a Mouse Model of Parkinson's Disease. Int J Mol Sci. 2020 Oct 15;21(20):7620. doi: 10.3390/ijms21207620. PMID: 33076300; PMCID: PMC7593947 |
1: Vakhitova YV, Kuzmina US, Voronin MV, Zainullina LF, Seredenin SB. Effect of Fabomotizole on Brain Gene Expression in MR Rats in the Open Field Test. Dokl Biochem Biophys. 2019 Sep;488(1):313-315. doi: 10.1134/S1607672919050090. Epub 2019 Nov 25. PMID: 31768849.
2: Tsorin IB, Barchukov VV, Vititnova MB, Kryzhanovskii SA, Seredenin SB. Anti- Ischemic Activity of Fabomotizole Hydrochloride under Conditions of Endothelial Dysfunction. Bull Exp Biol Med. 2019 Sep;167(5):634-636. doi: 10.1007/s10517-019-04586-x. Epub 2019 Nov 8. PMID: 31705224.
3: Kryzhanovskii SA, Tsorin IB, Stolyaruk VN, Vititnova MB, Ionova EO, Barchukov VV, Kozhevnikova LM, Seredenin SB. Examination of Cardioprotective Effects of Fabomotizole Hydrochloride in Translational Rat Model of Chronic Heart Failure. Bull Exp Biol Med. 2019 Nov;168(1):33-37. doi: 10.1007/s10517-019-04639-1. Epub 2019 Nov 18. PMID: 31741244.
4: Pérez-Villanueva J, Yépez-Mulia L, Rodríguez-Villar K, Cortés-Benítez F, Palacios-Espinosa JF, Soria-Arteche O. The giardicidal activity of lobendazole, fabomotizole, tenatoprazole and ipriflavone: A ligand-based virtual screening and in vitro study. Eur J Med Chem. 2021 Feb 5;211:113110. doi: 10.1016/j.ejmech.2020.113110. Epub 2020 Dec 17. PMID: 33360795.
5: Kryzhanovskii SA, Kozhevnikova LM, Tsorin IB, Sukhanova IF, Ionova EO, Stolyaruk VN, Vititnova MB, Miroshkina IA, Seredenin SB. On the Mechanism of the Cardioprotective Action of σ1 Receptor Agonist Anxiolytic Fabomotizole Hydrochloride (Afobazole). Bull Exp Biol Med. 2018 Sep;165(5):660-664. doi: 10.1007/s10517-018-4236-1. Epub 2018 Sep 17. PMID: 30225699.
6: Pogosova NV, Yufereva YM, Ausheva AK, Kursakov AA, Arutyunov AA, Boytsov SA. [The Possibility of Correcting Anxiety Symptoms in Cardiac Patients in Primary Care Settings: Results of the Therapeutic Part of a Russian Multicenter Study COMETA]. Kardiologiia. 2019 Sep 17;59(9):29-39. Russian. doi: 10.18087/cardio.2019.9.n468. PMID: 31540574.
7: Kryzhanovskii SA, Antipova TA, Vititnova MB, Nikolaev SV, Durnev AD. Angiogenic Effects of Anxiolytic Fabomotizole. Dokl Biochem Biophys. 2021 Mar;497(1):63-65. doi: 10.1134/S1607672921020101. Epub 2021 Apr 24. PMID: 33895918.
8: Voronin MV, Vakhitova YV, Tsypysheva IP, Tsypyshev DO, Rybina IV, Kurbanov RD, Abramova EV, Seredenin SB. Involvement of Chaperone Sigma1R in the Anxiolytic Effect of Fabomotizole. Int J Mol Sci. 2021 May 21;22(11):5455. doi: 10.3390/ijms22115455. PMID: 34064275.
9: Kolik LG, Nadorova AV, Stolyaruk VN, Miroshkina IA, Tsorin IB, Kryzhanovskii SA. Anxiolytic Properties of Trimetazidine in Experimental Models of Increased Anxiety. Bull Exp Biol Med. 2017 Mar;162(5):643-646. doi: 10.1007/s10517-017-3677-2. Epub 2017 Mar 31. PMID: 28361425.
10: Kryzhanovskii SA, Kozhevnikova LM, Vititnova MB, Efimova AO, Stolyaruk VN, Tsorin IB. On the Mechanism of Cardioprotective Effect of Fabomotizole in Alcoholic Cardiomyopathy. Bull Exp Biol Med. 2021 May;171(1):41-44. doi: 10.1007/s10517-021-05168-6. Epub 2021 May 29. PMID: 34050832.
11: Syunyakov TS, Neznamov GG. Otsenka terapevticheskoi effektivnosti i bezopasnosti selektivnogo anksiolitika afobazola pri generalizovannom trevozhnom rasstroistve i rasstroistvakh adaptatsii: rezul'taty mnogotsentrovogo randomizirovannogo sravnitel'nogo s diazepamom issledovaniya [Evaluation of the therapeutic efficacy and safety of the selective anxiolytic afobazole in generalized anxiety disorder and adjustment disorders: Results of a multicenter randomized comparative study of diazepam]. Ter Arkh. 2016;88(8):73-86. Russian. doi: 10.17116/terarkh201688873-86. PMID: 27636931.
