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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 information previously on 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, to run through November 2020.

According to a presentation at AAIC 2016, 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).

The main trial was completed in June 2022, with a final enrollment of 509. According to top-line results presented at the 2022 CTAD conference in San Francisco, both dose groups were combined and compared to placebo. Analyzed in this way, the drug was reported to slow decline on the ADAS-Cog by 45 percent and on the secondary CDR-SB by 27 percent. Graphs plotting the treatment and placebo group's values on outcome measures over time were not shown. Data was not presented for the co-primary, the ADCS-ADL. In the safety analysis, dizziness and confusion occurred in 25 and 13 percent of patients taking blarcamesine, respectively, compared to 5.6 and 2.5 percent in the placebo group (see slides).

This compound is also in development for Parkinson’s disease dementia and Rett Syndrome. Top-line results from a placebo-controlled, Phase 2 PDD study were presented at the 2020 CTAD conference. It enrolled 132 participants, and treatment with 30 or 50 mg daily for 14 weeks was reported to result in improvements in memory and attention measures compared to placebo. An open-label extension ran until June 2022. 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). A Phase 3 trial of 31 adult patients was completed in September 2021, and the company announced positive top-line results in February 2022 (press release), though the trial is mired in controversy (BusinessWire, BioSpace). A Phase 2/3 trial in 84 pediatric patients, began in July 2020 and is running until December 2022.

In November 2022, blarcamesine received Orphan Drug Designation from the U.S. FDA for Fragile X syndrome. The company has published positive preclinical results in mouse models of this disease (Cogram et al., 2022; Reyes et al., 2021).

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 2032 2033 2034
Anavex Life Science Corp. NCT02244541

Last Updated: 07 Dec 2022


  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. . Brain cell signaling abnormalities are detected in blood in a murine model of Fragile X syndrome and corrected by Sigma-1 receptor agonist Blarcamesine. Am J Med Genet A. 2022 Aug;188(8):2497-2500. Epub 2022 Jun 4 PubMed.
  4. . Effects of the sigma-1 receptor agonist blarcamesine in a murine model of fragile X syndrome: neurobehavioral phenotypes and receptor occupancy. Sci Rep. 2021 Aug 25;11(1):17150. PubMed.
  5. . 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.
  6. . 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.
  7. . 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

  2. AAIC 2016
  3. press release
  4. slides
  5. Dec 2020 press release
  6. press release
  7. BusinessWire
  8. BioSpace

Further Reading


  1. . Sigma receptor modulators: a patent review. Expert Opin Ther Pat. 2013 May;23(5):597-613. Epub 2013 Feb 7 PubMed.
  2. . The emerging role of the sigma-1 receptor in autophagy: hand-in-hand targets for the treatment of Alzheimer's. Expert Opin Ther Targets. 2021 May;25(5):401-414. Epub 2021 Jun 17 PubMed.
  3. . 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;296:270-8. Epub 2015 Sep 16 PubMed.
  4. . Sigma-1 Receptor Activation Induces Autophagy and Increases Proteostasis Capacity In Vitro and In Vivo. Cells. 2019 Mar 2;8(3) PubMed.
  5. . 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; PubMed.

External Resources

  1. Red flags fly over Anavex: What’s stopping the drug maker from enrolling U.S., European patients in trials?
  2. Lead Plaintiff Appointed in Anavex Fraud Suit