Synonym
Anavex-2-73; Anavex2-73; Anavex 2-73; Anavex-273; Anavex273; Anavex 273; AE-37 hydrochloride
IUPAC/Chemical Name
1-(2,2-diphenyltetrahydrofuran-3-yl)-N,N-dimethylmethanamine hydrochloride
InChi Key
FEQOLYDPQKHFTD-UHFFFAOYSA-N
InChi Code
InChI=1S/C19H23NO.ClH/c1-20(2)15-18-13-14-21-19(18,16-9-5-3-6-10-16)17-11-7-4-8-12-17;/h3-12,18H,13-15H2,1-2H3;1H
SMILES Code
CN(C)CC1C(C2=CC=CC=C2)(C3=CC=CC=C3)OCC1.[H]Cl
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
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
Biological target:
Blarcamesine hydrochloride (AVex-73 hydrochloride) is a Sigma-1 Receptor agonist with an IC50 of 860 nM.
In vitro activity:
As displayed in Figure 1, ANAVEX2-73 significantly induces autophagic flux when compared to control conditions. There is a concentration-dependent and significant increase in the autophagic flux following application of ANAVEX2-73: An increase of over 2-fold at 10 µM and over 1.5-fold at 1 µM ANAVEX2-73 (Figure 1A). As standard positive control to provoke the induction of autophagy, HeLa cells were incubated with EBSS medium, which resembles nutrient deprivation as autophagy stimulus.
Reference: Cells. 2019 Mar; 8(3): 211. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6468724/
In vivo activity:
Treatment with once daily administration of blarcamesine improved stride length at 8 and 12 weeks and front step length at 8 weeks only at the 30 mg/kg/day dose, with the latter effect completely restored relative to vehicle-treated WT mice (Fig. 2 top). The effect of treatment on front base width at 12 weeks was also significant (Fig. 2 bottom), in this instance by increasing the differences with the WT group (i.e., larger front base width).
Reference: Pharmacol Biochem Behav. 2019 Dec;187:172796. https://pubmed.ncbi.nlm.nih.gov/31704481/
|
Solvent |
mg/mL |
mM |
comments |
| Solubility |
| DMSO |
44.5 |
140.00 |
|
| Ethanol |
3.0 |
9.44 |
|
| Water |
64.0 |
201.35 |
|
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
317.86
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. Lisak RP, Nedelkoska L, Benjamins JA. Sigma-1 receptor agonists as potential protective therapies in multiple sclerosis. J Neuroimmunol. 2020 Feb 21;342:577188. doi: 10.1016/j.jneuroim.2020.577188. Epub ahead of print. PMID: 32179326.
2. Christ MG, Huesmann H, Nagel H, Kern A, Behl C. Sigma-1 Receptor Activation Induces Autophagy and Increases Proteostasis Capacity In Vitro and In Vivo. Cells. 2019 Mar 2;8(3):211. doi: 10.3390/cells8030211. PMID: 30832324; PMCID: PMC6468724.
3. Kaufmann WE, Sprouse J, Rebowe N, Hanania T, Klamer D, Missling CU. ANAVEX®2-73 (blarcamesine), a Sigma-1 receptor agonist, ameliorates neurologic impairments in a mouse model of Rett syndrome. Pharmacol Biochem Behav. 2019 Dec;187:172796. doi: 10.1016/j.pbb.2019.172796. Epub 2019 Nov 5. PMID: 31704481.
4. Lahmy V, Long R, Morin D, Villard V, Maurice T. Mitochondrial protection by the mixed muscarinic/σ1 ligand ANAVEX2-73, a tetrahydrofuran derivative, in Aβ25-35 peptide-injected mice, a nontransgenic Alzheimer's disease model. Front Cell Neurosci. 2015 Jan 20;8:463. doi: 10.3389/fncel.2014.00463. PMID: 25653589; PMCID: PMC4299448.
In vitro protocol:
1. Lisak RP, Nedelkoska L, Benjamins JA. Sigma-1 receptor agonists as potential protective therapies in multiple sclerosis. J Neuroimmunol. 2020 Feb 21;342:577188. doi: 10.1016/j.jneuroim.2020.577188. Epub ahead of print. PMID: 32179326.
2. Christ MG, Huesmann H, Nagel H, Kern A, Behl C. Sigma-1 Receptor Activation Induces Autophagy and Increases Proteostasis Capacity In Vitro and In Vivo. Cells. 2019 Mar 2;8(3):211. doi: 10.3390/cells8030211. PMID: 30832324; PMCID: PMC6468724.
In vivo protocol:
1. Kaufmann WE, Sprouse J, Rebowe N, Hanania T, Klamer D, Missling CU. ANAVEX®2-73 (blarcamesine), a Sigma-1 receptor agonist, ameliorates neurologic impairments in a mouse model of Rett syndrome. Pharmacol Biochem Behav. 2019 Dec;187:172796. doi: 10.1016/j.pbb.2019.172796. Epub 2019 Nov 5. PMID: 31704481.
2. Lahmy V, Long R, Morin D, Villard V, Maurice T. Mitochondrial protection by the mixed muscarinic/σ1 ligand ANAVEX2-73, a tetrahydrofuran derivative, in Aβ25-35 peptide-injected mice, a nontransgenic Alzheimer's disease model. Front Cell Neurosci. 2015 Jan 20;8:463. doi: 10.3389/fncel.2014.00463. PMID: 25653589; PMCID: PMC4299448.
1: Goguadze N, Zhuravliova E, Morin D, Mikeladze D, Maurice T. Sigma-1 Receptor Agonists Induce Oxidative Stress in Mitochondria and Enhance Complex I Activity in Physiological Condition but Protect Against Pathological Oxidative Stress. Neurotox Res. 2017 Nov 10. doi: 10.1007/s12640-017-9838-2. [Epub ahead of print] PubMed PMID: 29127580.
2: Maurice T. Protection by sigma-1 receptor agonists is synergic with donepezil, but not with memantine, in a mouse model of amyloid-induced memory impairments. Behav Brain Res. 2016 Jan 1;296:270-278. doi: 10.1016/j.bbr.2015.09.020. Epub 2015 Sep 16. PubMed PMID: 26386305.
3: Mason VL. Alzheimer's Association International Conference on Alzheimer's Disease 2015 (AAIC 2015) (July 18-23, 2015 - Washington, D.C., USA). Drugs Today (Barc). 2015 Jul;51(7):447-52. doi: 10.1358/dot.2015.51.7.2375989. PubMed PMID: 26261847.
4: Lahmy V, Long R, Morin D, Villard V, Maurice T. Mitochondrial protection by the mixed muscarinic/σ1 ligand ANAVEX2-73, a tetrahydrofuran derivative, in Aβ25-35 peptide-injected mice, a nontransgenic Alzheimer's disease model. Front Cell Neurosci. 2015 Jan 20;8:463. doi: 10.3389/fncel.2014.00463. eCollection 2014. PubMed PMID: 25653589; PubMed Central PMCID: PMC4299448.
5: Lahmy V, Meunier J, Malmström S, Naert G, Givalois L, Kim SH, Villard V, Vamvakides A, Maurice T. Blockade of Tau hyperphosphorylation and Aβ₁₋₄₂ generation by the aminotetrahydrofuran derivative ANAVEX2-73, a mixed muscarinic and σ₁ receptor agonist, in a nontransgenic mouse model of Alzheimer's disease. Neuropsychopharmacology. 2013 Aug;38(9):1706-23. doi: 10.1038/npp.2013.70. Epub 2013 Mar 14. PubMed PMID: 23493042; PubMed Central PMCID: PMC3717544.
6: Villard V, Espallergues J, Keller E, Vamvakides A, Maurice T. Anti-amnesic and neuroprotective potentials of the mixed muscarinic receptor/sigma 1 (σ1) ligand ANAVEX2-73, a novel aminotetrahydrofuran derivative. J Psychopharmacol. 2011 Aug;25(8):1101-17. doi: 10.1177/0269881110379286. Epub 2010 Sep 9. PubMed PMID: 20829307.
