Exploring the Role of Sigma-1 Receptors in Memory Enhancement by ANAVEX1-41: Insights from Aminotetrahydrofuran Derivative

ANAVEX1-41 is a compound that shows strong binding to muscarinic and sigma-1 receptors. Sigma-1 receptors are known to influence glutamate and acetylcholine activity in the brain, and their activation can lead to memory and mood improvements. The study examines the role of sigma-1 receptors in the effects of ANAVEX1-41 on behavior.

In laboratory tests, ANAVEX1-41 demonstrated high affinity for muscarinic receptors, particularly M1, M3, M4, and M2, and was a selective ligand for sigma-1 receptors. When tested in mice, the drug did not affect learning when administered alone but was effective in reducing memory impairment caused by scopolamine, with the optimal dose being 0.1 mg/kg. The anti-amnesia effect was blocked by the sigma-1 antagonist BD1047 and by pretreatment with a sigma-1 receptor-targeted antisense oligodeoxynucleotide, particularly in long-term memory tests.

Furthermore, ANAVEX1-41 was found to reduce signs of depression-like behavior in mice at doses of 30 and 60 mg/kg, an effect that did not seem to involve sigma-1 receptors as it was not affected by BD1047 or the antisense treatment.

The study concludes that ANAVEX1-41 has potential as an anti-amnesia drug, with its effects mediated through both muscarinic and sigma-1 receptors, the latter possibly playing a role in enhancing long-term memory. The research was published in the British Journal of Pharmacology in 2007.