Chemical Name: Tetrahydro-N,N-dimethyl-2,2-diphenyl-3-furanmethanamine hydrochloride
Therapy Type: Small Molecule (timeline)
Target Type: Other (timeline)
Condition(s): Alzheimer's Disease
U.S. FDA Status: Alzheimer's Disease (Phase 2)
Company: Anavex Life Science Corp.
This compound is an agonist of the intracellular sigma-1 chaperone protein. Specifically, it is a mixed ligand for sigma1/muscarinic receptors. Expressed in most tissues and located at focal contacts between mitochondria and the endoplasmic reticulum, the sigma-1 receptor forms heterodimers with many other membrane receptors, and as such influences multiple cellular pathways and physiological processes. Anavex 2-73 reportedly binds the sigma-1 receptor in the high nanomolar and the muscarinic receptor in the low micromolar range.
The compound has been reported to have memory-preserving and neuroprotective effects in mice treated with the muscarinic receptor antagonist scopolamine, with synthetic Aβ oligomer injection, or with the NMDA receptor agonist dizocilpine (Villard et al., 2011). A recent study suggested that Anavex 2-73 may block tau hyperphosphorylation (see Jan 2013 conference news and Lahmy et al., 2013).
According to its website, Anavex conducted an initial Phase 1 study in healthy men in Germany that claimed to determine a maximal tolerated dose of 55 mg.
In August 2014, the company listed a Phase 2a study that was to compare oral and intravenous doses in a two-phase, 36-day crossover design followed by a 6-month extension. The study design was originally registered as double blind, though the treatment descriptions were open-label. It was to enroll 32 people with mild to moderate AD whose clinical diagnosis is consistent with findings on a CT or MRI scan. Intervention was to consist of a 36-day period of either daily oral doses or daily infusions, which cross over to the other delivery mode at midpoint, followed by six months of once daily oral dosing. The stated primary outcome was to determine the maximum tolerated dose. Secondary outcomes included pharmacokinetic blood tests as well as various efficacy measures such as MMSE, ADCS-ADLs, and EEG. This trial is being conducted in Melbourne, Australia. It uses no placebo control.
According to the clinicaltrials.gov changes record, in October 2014 Anavex entered changes switching study design to open-label, reducing the number of arms from 8 to 4, and reducing the number of exclusion criteria from 23 to four, with investigator discretion added. The study started recruiting in December 2014. In September 2015 the follow-up period of daily dosing was lengthened from six to 12 months (see clinicaltrials.gov changes record).
For all listed trials on Anavex 2-73, see clinicaltrials.gov.
Clinical Trial Timeline
- Phase 2
- Study completed / Planned end date
- Planned end date unavailable
- Study aborted
|Anavex Life Science Corp.||NCT02244541||
Last Updated: 15 Jan 2016
- 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. PubMed.
- 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 Mar 14; PubMed.