Blarcamesine

Blarcamesine is an agonist of the sigma non-opioid intracellular receptor 1 (σ₁ receptor).¹ It inhibits reductions in mitochondrial oxygen consumption and lipid peroxidation induced by amyloid-β (Aβ) (25-35) (Aβ (25-35)) in isolated mouse hippocampus when administered at a dose of 1 mg/kg. Blarcamesine (1 mg/kg) improves deficits in novel object recognition induced by Aβ (25-35) in mice, as well as reduces tau phosphorylation and Aβ (1-42) levels in the hippocampus in the same model.² It increases the latency to fall in the rotarod test, reduces gait impairments, and reduces increases in the mean acoustic startle response in an Mecp2^-/- mouse model of Rett syndrome, an X-linked neurodevelopmental disorder, when administered at a dose of 30 mg/kg per day.³

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1. Lahmy, V., Long, R.M., Morin, D., et al. 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. 8, 463 (2015).

2. Lahmy, V., Meunier, J., Malström, S., et al. 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 38(9), 17061723 (2013).

3. Kaufmann, W., Sprouse, J., Rebowe, N., et al. ANAVEX^®2-73 (blarcamesine), a Sigma-1 receptor agonist, ameliorates neurologic impairments in a mouse model of Rett syndrome. Pharmacol. Biochem. Behav. 187, 172796 (2019).