European journal of pharmacology
March 5, 2024
Hugo R Arias, Deborah Rudin, Dustin J Hines et al.
12 citations
A non-hallucinogenic compound derived from ibogamine, DM506, produces anxiolytic- and sedative-like effects in mice without causing hallucinogenic head-twitch responses. At 15 mg/kg, DM506 induces both acute and long-lasting anxiety-reducing behavior in naive and stressed mice. Repeated 5 mg/kg doses show no cumulative effects or side effects. Higher doses (40 mg/kg) cause sedation that is blocked by the 5-HT2A receptor antagonist volinanserin. DM506 binds to human 5-HT2A (Ki = 24 nM) and 5-HT2B (Ki = 16 nM) receptors, activating them with EC50 values of 9 nM and 3 nM, respectively, acting as a partial agonist compared to the full agonist DOI. Electroencephalography shows increased transition from alert to deep-sleep brain wave activity.
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.
Progress in neuro-psychopharmacology & biological psychiatry
July 13, 2025
Jasmine Jade Butler, Margherita Virgili, Giuseppe Di Giovanni et al.
5 citations
Serotonergic psychedelics disrupt the normally organized pattern of correlations among serotonin, dopamine, and noradrenaline concentrations across 28 brain regions in mice during forced exploratory behavior. Both the 5-HT2A receptor agonist TCB-2 and the antagonist MDL-100,907 decreased correlations between regional neurochemical levels, while combining them partially restored those correlations. TCB-2 dose-dependently reduced serotonin turnover across all brain regions and dopamine turnover in the striatum, and enhanced markers of dopamine and noradrenaline systems in the anterior cingulate cortex. MDL-100,907 alone had minimal effects on monoamine levels but reduced TCB-2-induced head twitches and increased monoamine concentrations in the anterior cingulate cortex without affecting the serotonin turnover decrease. The functional connectivity of monoaminergic systems during exploration is highly sensitive to modulation through 5-HT2A receptor activation or blockade.