Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
June 17, 2024
Hugo R. Arias, L. Micheli, Deborah Rudin et al.
14 citations
New non-hallucinogenic iboga alkaloid derivatives, called ibogalogs (TBG, IBG, and DM506), reduce pain hypersensitivity in mouse models of neuropathic and visceral pain. IBG provided the longest pain relief at a lower dose, while DM506 acted fastest. The pain-relieving effect was blocked by the 5-HT2A receptor antagonist ketanserin, indicating that activation of the 5-HT2A receptor, not its inhibition, mediates this activity. Ibogalogs activate 5-HT2A and 5-HT6 receptors and act as inverse agonists (except TBG) at the 5-HT7 receptor. Based on prior work, 5-HT6 inhibition and 5-HT7 activation relieve pain, so these receptors are not involved. The anti-hypersensitivity activity of ibogalogs in mice is mediated by 5-HT2A receptor activation.
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.
The FASEB Journal
April 1, 2012
Ilana Emert, Katarzyna M. Targowska‐duda, Dominik Feuerbach et al.
Ibogaine inhibits calcium influx through human α3β4 nicotinic acetylcholine receptors with roughly nine times higher potency than phencyclidine (PCP). Radioligand binding shows ibogaine binds to a single site on the receptor with a dissociation constant of 0.46 μM, and it has slightly higher affinity for desensitized receptors than for resting ones. Docking studies indicate both compounds interact with a binding domain between the serine (position 6′) and valine/phenylalanine (position 13′) rings, primarily through van der Waals contacts, consistent with the measured enthalpic contribution. Entropic contributions suggest local conformational changes upon binding.