Nature
June 1, 2024
Audrey L Warren, David Lankri, Michael J Cunningham et al.
74 citations
Psychedelic substances like LSD and psilocybin show potential for treating neuropsychiatric disorders, primarily acting through the serotonin 5-HT2A receptor. However, 5-HT1A also contributes to the effects of tryptamine hallucinogens, especially 5-MeO-DMT from Colorado River toad toxin. Using cryo-EM structures, medicinal chemistry, and mouse behavior, researchers mapped how 5-MeO-DMT engages 5-HT1A. They characterized molecular determinants of signaling potency, efficacy, and selectivity at both 5-HT1A and 5-HT2A. A 5-HT1A-selective analogue of 5-MeO-DMT lacked hallucinogenic effects but retained anxiolytic-like and antidepressant-like activity in socially defeated animals, uncovering molecular aspects that may aid developing new neuropsychiatric medications.
ACS chemical neuroscience
June 3, 2020
Paola Rodrı Guez, Jessika Urbanavicius, José Pedro Prieto et al.
44 citations
Ibogaine and its main metabolite noribogaine produce antidepressant-like effects in rats, as measured by the forced swim test. Both compounds induced a dose- and time-dependent reduction in immobility without altering locomotor activity. Noribogaine's effect was short-lived (30 minutes) and correlated with high brain concentrations (estimated >8 μM free drug), while ibogaine's effect was significant at 3 hours, when both ibogaine (~0.5 μM) and noribogaine (~2.5 μM) were present at concentrations that alone could not produce the same outcome. The findings suggest a polypharmacological mechanism underlies the antidepressant-like effects.
Journal of pharmaceutical and biomedical analysis
June 24, 2026
Scot Mcintosh, Isabella Maldonado, Nickalus C Smith et al.
A sensitive UPLC-MS/MS method was developed and validated to quantify ibogaine, noribogaine, ibogamine, and oxa-noribogaine in rat brain microdialysate, measuring pharmacologically active, unbound drug in brain extracellular fluid rather than total tissue content. The method achieved lower limits of quantification of 0.78-1.56 ng/mL with a 6-minute run time, and calibration curves were linear over 0.78-75 ng/mL for ibogamine and 1.56-75 ng/mL for the other analytes. Accuracy and precision met acceptance criteria. Applied to rats (n=4), noribogaine in nucleus accumbens after 10 mg/kg intraperitoneal administration reached a peak unbound concentration of 292 ± 68 ng/mL at 50 minutes, demonstrating suitability for real-time neuropharmacokinetic profiling of iboga alkaloids.