Name: Blarcamesine
Synonyms: Anavex 2-73
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, Parkinson's Disease Dementia, Parkinson's Disease
U.S. FDA Status: Alzheimer's Disease (Phase 2/3), Parkinson's Disease Dementia (Phase 2), Parkinson's Disease (Phase 1)
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. Blarcamesine 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). Other studies in the Aβ oligomer injection model suggest that blarcamesine may block tau hyperphosphorylation and protect mitochondria (Jan 2013 conference newsLahmy et al., 2013Lahmy et al., 2014).


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 six-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 was consistent with findings on a CT or MRI scan. Intervention was to consist of a five-week 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 changes record, in October 2014 Anavex entered changes switching study design to open-label, reducing the number of arms from eight to four, 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 changes record). In October 2019, the company added a four-year open-label extension.

According to a presentation at AAIC 2106, after 31 weeks of dosing in 28 patients, the drug met safety endpoints. Most adverse events were mild or moderate, with headache and dizziness the most frequent.  Most people took 20 or 30 mg daily; the maximum tolerated dose was 48 mg. Scores on MMSE and ADCS-ADL remained steady. A subsequent paper showed safety to have been maintained out to 148 weeks. Statistical modeling of complete trial data linked changes in MMSE and ACDS-ADL scores over 57 weeks with blood blarcamesine levels, baseline MMSE, and genetic variants in the sigma receptor gene and catechol-O-methyltransferase genes (Hampel et al., 2020).

In July 2018, a Phase 2b/3 trial at 16 sites in Australia began enrolling 450 people with mild cognitive impairment or early dementia, plus PET or CSF confirmation of AD pathology. Participants are randomized to high- or low-dose blarcamesine or placebo, taken as capsules once daily for 48 weeks. The primary outcomes are change in ADAS-Cog and ADCS-ADL, safety, and tolerability. Secondary measures include CDR- SB, structural and functional MRI, and sleep score. The trial assesses blood and CSF concentrations of Aβ40, Aβ42, total and phosphorylated tau, NfL, YKL-40, neurogranin, and BACE1. A subgroup analysis is planned based on participants’ sigma receptors and COMT genotype. In October 2019, Anavex added a two-year, open-label safety extension and, in  June 2020, it announced the trial would expand to sites in the United Kingdom and Canada (see press release).

This compound is also in development for Parkinson’s disease dementia and Rett Syndrome. Topline results from a placebo-controlled, Phase 2 PDD study were presented at the 2020 CTAD conference. It 132 enrolled participants; treatment with 30 or 50 mg daily for 14 weeks resulted in improvements in memory and attention measures compared to placebo. The trial is continuing in an open-label extension. Anavex in February 2021 received Michael J Fox Foundation funding for a pharmacokinetics/CNS exposure study in 24 people with Parkinson's disease.

For Rett Syndrome (Kaufmann et al., 2019), Anavex announced symptomatic improvements for a 31-patient Phase 2 study (Dec 2020 press release). Another Phase 2 trial, and a Phase 2/3 trial of 69 participants, are enrolling.

For trial details, see

Clinical Trial Timeline

  • Phase 2
  • Study completed / Planned end date
  • Planned end date unavailable
  • Study aborted
Sponsor Clinical Trial 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 2023 2024 2025 2026 2027 2028 2029 2030 2031
Anavex Life Science Corp. NCT02244541

Last Updated: 24 Feb 2021


  1. The protocol or trial design or entry criteria were never changed after trial approval by the ethics committee, with the exception of extending Part B from 26 to 52 weeks. The first input into was performed by a new CRO member, who was not familiar with the specific entry templates into, hence this had to be corrected to accurately reflect the particulars of the trial.

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News Citations

  1. Zuers—Αlpha, Beta, Sigma: Which Will Yield New AD Drug?

Paper Citations

  1. . A precision medicine framework using artificial intelligence for the identification and confirmation of genomic biomarkers of response to an Alzheimer's disease therapy: Analysis of the blarcamesine (ANAVEX2-73) Phase 2a clinical study. Alzheimers Dement (N Y). 2020;6(1):e12013. Epub 2020 Apr 19 PubMed.
  2. . 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. Epub 2019 Nov 5 PubMed.
  3. . 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.
  4. . 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.
  5. . 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. 2014;8:463. Epub 2015 Jan 20 PubMed.

External Citations

  1. website
  3. AAIC 2106
  4. press release
  5. Dec 2020 press release

Further Reading


  1. . Sigma receptor modulators: a patent review. Expert Opin Ther Pat. 2013 May;23(5):597-613. Epub 2013 Feb 7 PubMed.