A5022631404- Neurotransmitter Receptor Influence on Behavior
- Psychedelics and Drug Studies
- Chemical synthesis and alkaloids
- Neuroscience and Neuropharmacology Research
- Memory and Neural Mechanisms
- Biochemical Analysis and Sensing Techniques
- Neuroendocrine regulation and behavior
- Receptor Mechanisms and Signaling
- Stress Responses and Cortisol
- Plant and fungal interactions
- Treatment of Major Depression
- Tryptophan and brain disorders
- Pain Mechanisms and Treatments
- Alkaloids: synthesis and pharmacology
- Functional Brain Connectivity Studies
- Bipolar Disorder and Treatment
- Olfactory and Sensory Function Studies
- Nicotinic Acetylcholine Receptors Study
University of California, San Diego
2019-2023
University of California, Santa Barbara
2015-2019
Behavioral Pharma (United States)
2015-2018
Serotonergic psychedelics possess considerable therapeutic potential. Although 5-HT2A receptor activation mediates psychedelic effects, prototypical activate both 5-HT2A-Gq/11 and β-arrestin2 transducers, making their respective roles unclear. To elucidate this, we develop a series of 5-HT2A-selective ligands with varying Gq efficacies, including β-arrestin-biased ligands. We show that 5-HT2A-Gq but not 5-HT2A-β-arrestin2 recruitment efficacy predicts potential, assessed using head-twitch...
The 5-HT2A receptor is thought to be the primary target for psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine) and other serotonergic hallucinogens (psychedelic drugs). Although a large amount of experimental work has been conducted characterize pharmacology its dephosphorylated metabolite psilocin (4-hydroxy-N,N-dimethyltryptamine), there little systematic investigation structure-activity relationships (SAR) 4-substituted tryptamine derivatives. In addition, structural analogs containing...
The psychedelic properties of lysergic acid diethylamide (LSD) have captured the imagination researchers for many years and its rediscovery as an important research tool is evidenced by clinical use within neuroscientific therapeutic settings. At same time, a number novel LSD analogs recently emerged recreational drugs, which makes it necessary to study their analytical pharmacological properties. One recent addition this series 1-butanoyl-LSD (1B-LSD), constitutional isomer...
A general synthetic method was developed to access known tryptamine natural products present in psilocybin-producing mushrooms. In vitro and vivo experiments were then conducted inform speculations on the psychoactive properties, or lack thereof, of products. animal models, psychedelic activity by baeocystin alone not evident using mouse head twitch response assay, despite its putative dephosphorylated metabolite, norpsilocin, possessing potent agonist at 5-HT2A receptor.
Abstract Lysergic acid diethylamide (LSD) is a prototypical serotonergic psychedelic drug and the subject of many clinical investigations. In recent years, range lysergamides has emerged with production some being inspired by existing scientific literature. Others, for example various 1‐acyl substituted lysergamides, did not exist before their appearance as research chemicals. 1‐Cylopropanoyl‐LSD (1CP‐LSD) recently new addition to group lysergamide‐based designer drugs believed be...
Serotonergic psychedelics possess considerable therapeutic potential. Although 5-HT2A receptor activation mediates psychedelic effects, prototypical activate both 5-HT2A-Gq/11 and β-arrestin2 signaling, making their respective roles unclear. To elucidate this, we developed a series of 5-HT2A-selective ligands with varying Gq efficacies, including β-arrestin-biased ligands. We show that 5-HT2A-Gq but not 5-HT2A-β-arrestin2 efficacy predicts potential, assessed using head-twitch response (HTR)...
Abstract The NMDA receptor (NMDAR) antagonist ketamine has shown great potential as a rapid-acting antidepressant; however, its use is limited by poor oral bioavailability and side effect profile that necessitates in-clinic dosing. GM-1020 novel NMDAR was developed to address these limitations of treatment for depression. Here, we present the preclinical characterization alongside ketamine, comparison. In vitro, profiled binding functional inhibition using patch-clamp electrophysiology....
The 2,5-dimethoxyphenethylamine (2,5-PEA) scaffold is recognized as a motif conferring potent agonist activity at the serotonin 2A receptor (5-HT2AR). 2,5-dimethoxy present in several classical phenethylamine psychedelics such 2,4,5- trimethoxyamphetamine (TMA-2), 2,5-dimethoxy-4-methylamphetamine (DOM), 2,5-dimethoxy-4-iodoamphetamine (DOI), 2,5- dimethoxy-4-bromoamphetamine (DOB), 2,5-dimethoxy-4-bromophenethylamine (2C-B), and 2,5-dimethoxy-4-iodophenethylamine (2C-I), it has previously...