Anavex Life Sciences Corp. is a pharmaceutical company that develops drug candidates.ANAVEX 2-73 has been shown to provide protection from oxidative stress, which damages and destroys neurons and is believed to be a primary cause of Alzheimer's disease. Research in recent years indicates that oxidative stress is a precursor to amyloid-beta plaques and tau , and could be a novel and appropriate therapeutic target. Wikipedia.
Papanastasiou I.,National and Kapodistrian University of Athens |
Tsotinis A.,National and Kapodistrian University of Athens |
Kolocouris N.,National and Kapodistrian University of Athens |
Nikas S.P.,Northeastern University |
And 2 more authors.
Medicinal Chemistry Research | Year: 2014
1-Benzyl-2-aminoadamantanes 2a-c, conformationally constrained aminoadamantanes 3a, b and 4 and diaminoadamantanes derivatives 5a-c, 6a-c were synthesized and tested as antiproliferative agents. The in vitro biological evaluation showed a significant difference in activity between 1-phenyl and 1-benzyl derivatives. © Springer Science+Business Media 2013. Source
Villard V.,Montpellier University |
Villard V.,EPHE Paris |
Espallergues J.,Montpellier University |
Espallergues J.,EPHE Paris |
And 5 more authors.
Journal of Psychopharmacology | Year: 2011
Tetrahydro-N, N-dimethyl-2, 2-diphenyl-3-furanmethanamine hydrochloride (ANAVEX2-73) binds to muscarinic acetylcholine and sigma1 (σ1) receptors with affinities in the low micromolar range. We characterized its anti-amnesic and neuroprotective potentials in pharmacological and pathological amnesia models. Spatial working memory was evaluated using spontaneous alternation in the Y-maze and non-spatial memory using passive avoidance procedures. ANAVEX2-73 (0.01-3.0 mg/kg i.p.) alleviated the scopolamine- and dizocilpine-induced learning impairments. ANAVEX2-73 (300 μg/kg) also reversed the learning deficits in mice injected with Aβ25-35 peptide, a non-transgenic Alzheimer's disease model. When the drug was injected simultaneously with Aβ25-35, 7 days before the tests, it blocked the appearance of learning impairments. This protective activity was confirmed since ANAVEX2-73 blocked the Aβ25-35-induced oxidative stress in the hippocampus. This effect was differentially sensitive to the muscarinic receptor antagonist scopolamine or the σ1 protein antagonist BD1047, confirming the mixed muscarinic/σ1 pharmacological action. Finally, its unique demethyl metabolite, ANAVEX19-144, was also effective and ANAVEX2-73 presented a longer duration of action, effective 12 h before Aβ25-35, than its related compound ANAVEX1-41. The neuroprotective activity of ANAVEX2-73, its mixed cholinergic/σ1 activity, its low active dose range and its long duration of action together reinforce its therapeutic potential in Alzheimer's disease. © The Author(s) 2011 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav. Source
Anavex | Date: 2013-07-12
This invention concerns a dosage form comprising a therapeutically neuroprotective amount of A2-73 and a neuroprotective amount of at least one cooperating acetylcholinesterase inhibitor selected from the group consisting of donepezil, galantamine, rivastigmine, or memantine and method of use.
Anavex | Date: 2015-09-25
Pharmaceutical preparations for the treatment of neurological conditions including Alzheimers disease.
Blockade of tau hyperphosphorylation and aβ 1-42 generation by the aminotetrahydrofuran derivative ANAVEX2-73, a mixed muscarinic and σ 1 receptor agonist, in a nontransgenic mouse model of Alzheimer's disease
Lahmy V.,Montpellier University |
Lahmy V.,EPHE Paris |
Meunier J.,Amylgen |
Malmstrom S.,Amylgen |
And 9 more authors.
Neuropsychopharmacology | Year: 2013
The main objective of the present study was to establish whether the mixed σ 1/muscarinic ligand ANAVEX2-73, shown to be neuroprotective in Alzheimer's disease (AD) models in vivo and currently in clinical phase I/IIa, could have the ability to reduce the appearance of hyperphosphorylated Tau and amyloid-β1-42 (Aβ1-42) in the Aβ 25-35 mouse model of AD. We therefore first confirmed that Aβ 25-35 injection induced hyperphosphorylation of Tau protein, by showing that it rapidly decreased Akt activity and activated glycogen synthase kinase-3β (GSK-3β) in the mouse hippocampus. Second, we showed that the kinase activation, and resulting Tau alteration, directly contributed to the amyloid toxicity, as co-administration of the selective GSK-3β inhibitor 2-thio(3-iodobenzyl)-5-(1-pyridyl)-[1,3,4]-oxidiazole blocked both Tau phosphorylation and Aβ 25-35-induced memory impairments. Third, we analyzed the ANAVEX2-73 effect on Tau phosphorylation and activation of the related kinase pathways (Akt and GSK-3β). And fourth, we also addressed the impact of the drug on Aβ 25-35-induced Aβ1-42 seeding and observed that the compound significantly blocked the increase in Aβ1-42 and C99 levels in the hippocampus, suggesting that it may alleviate amyloid load in AD models. The comparison with PRE-084, a selective and reference σ 1 receptor agonist, and xanomeline, a muscarinic ligand presenting similar profile as ANAVEX2-73 on M1 and M2 subtypes, confirmed that both muscarinic and σ 1 targets are involved in the ANAVEX2-73 effects. The drug, acting synergistically on both targets, but with moderate affinity, presents a promising pharmacological profile. © 2013 American College of Neuropsychopharmacology. All rights reserved. Source