Ibogalogs improve spatial and recognition memory in rodents through a mechanism involving 5-HT2A receptor activation-enhanced NMDA receptor activity in hippocampal pyramidal CA1 neurons
Biomedicine & Pharmacotherapy November 13, 2025 Abdeslam Chagraoui, Luis A Haro Santillan, Renata Bocian et al. 5 citations
Ibogalogs, particularly DM506 and IBG, improve short- and long-term spatial memory in mice, while DM506 alone enhances long-term recognition memory. Tabernanthalog (TBG) showed less efficacy. These memory enhancements involve serotonin 5-HT2A and 2C receptors, as antagonists partially blocked the effects. Electrophysiological experiments linked ibogalogs to hippocampal function: TBG and DM506 increased theta rhythm power and amplitude in CA1, while volinanserin and high DM506 concentrations decreased them. DM506 enhanced NMDAR-mediated currents in CA1 neurons (EC50 = 20 ± 15 nM), blocked by Mg2+. TBG had a lower effect at high concentrations. The findings indicate ibogalogs enhance memory via 5-HT2A/2CR activation, modulating NMDAR activity and theta rhythm in hippocampal CA1.