ACS Medicinal Chemistry LettersFebruary 8, 2024Navoda Jayakodiarachchi, Mallory A Maurer, Daniel C Schultz et al.6 citations
Herein, we report the synthesis and characterization of a novel set of substituted indazole-ethanamines and indazole-tetrahydropyridines as potent serotonin receptor subtype 2 (5-HT2) agonists. Specifically, we examine the 5-HT2 pharmacology of the direct indazole analogs of 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) and related serotonergic tryptamines, and highlight the need for rigorous...
Microdosing ketamine is a novel antidepressant for treatment‐resistant depression. Traditional antidepressants, like selective serotonin reuptake inhibitors (SSRIs), inhibit serotonin reuptake, but it is not clear if ketamine shows a similar mechanism. Here, we tested the effects of feeding ketamine and SSRIs to Drosophila melanogaster larvae, which has a similar serotonin system to mammals and...
The introduction of arylmethyl substituents on the amine nitrogen atom of phenethylamines and tryptamines often results in profound increases in their affinity and functional activity at 5-HT2 serotonin receptors. To probe the sensitivity of this effect to substantially larger N-substituents, ten derivatives of the well-characterized psychedelic phenethylamine 2C-B were prepared by appending...
This systematic review and a meta-analysis synthesised the results from contemporary, randomized and non-randomized controlled studies to assess lasting (one week minimum) changes on cognition/creativity, emotional processing and personality from serotonergic psychedelics. PubMed, Embase and PsycInfo were searched in July 2022. Risk of bias was assessed using Rob 2.0 and ROBINS-I. Ten studies...
Psychedelic drugs, which share in common 5-HT2A receptor agonist activity, have shown promise in treating alcohol-use disorders (AUDs). Repeated exposure to ethanol (EtOH) induces molecular and behavioural changes reflective of neuroadaptations that may contribute to addiction. Psychedelic drugs can induce neuroplasticity also, raising the possibility that their potential clinical effects in...
Psychedelic compounds, including psilocybin, LSD (lysergic acid diethylamide), DMT (N,N -dimethyltryptamine), and 5-MeO-DMT (5-methoxy-N,N-dimethyltryptamine), all of which are serotonin 2A receptor agonists, are being investigated as potential treatments. This review aims to summarize the current clinical research on these 4 compounds and mescaline to guide future research. Their mechanism(s)...
Background: There is growing evidence for the therapeutic effects of psychedelics. However, it is still uncertain how these drugs interact with serotonergic antidepressants (serotonin reuptake inhibitors (SRIs)). Objective: This study explores the interaction between psychedelics and SRIs in terms of therapeutic effects. The objective is to compare acute psychedelic effects and subsequent...
Functional selectivity in the context of serotonin 2A (5-HT 2A ) receptor agonists is often described as differences psychedelic compounds have in the activation of Gq vs β-arrestin signaling in the brain and how that may relate to inducing psychoactive and hallucinatory properties with respect to each other. However, the presence of 5-HT 2A receptors throughout the body in several cell types,...
Noribogaine (noribo) is the primary metabolite from ibogaine, an atypical psychedelic alkaloid isolated from the root bark of the African shrub Tabernanthe iboga. The main objective of this study was to test the hypothesis that molecular, electrophysiological, and behavioral responses of noribo are mediated by the 5-HT2A receptor (5-HT2AR) in mice. In that regard, we used male and female,...
RESUMEN El síndrome serotoninérgico es un conjunto de signos y síntomas generados por hiperactividad serotoninérgica, caracterizado principalmente por alteración del sistema nervioso central. La medicina tradicional, históricamente utiliza herbales con fines curativos y religiosos que podrían tener efectos sobre el sistema serotoninérgico, receptores de dopamina, glutamato y noradrenalina, en...