A5049499127- Neurotransmitter Receptor Influence on Behavior
- Psychedelics and Drug Studies
- Pharmacological Receptor Mechanisms and Effects
- Chemical synthesis and alkaloids
- Circadian rhythm and melatonin
- Pain Mechanisms and Treatments
- Forensic Toxicology and Drug Analysis
- Receptor Mechanisms and Signaling
- Crystallization and Solubility Studies
- Veterinary Pharmacology and Anesthesia
- X-ray Diffraction in Crystallography
- Neuropeptides and Animal Physiology
- Nicotinic Acetylcholine Receptors Study
- Sleep and Wakefulness Research
- Health, Environment, Cognitive Aging
- Asthma and respiratory diseases
- Diet and metabolism studies
- RNA Research and Splicing
- Neuroendocrine regulation and behavior
- Poisoning and overdose treatments
- Alkaloids: synthesis and pharmacology
- Cannabis and Cannabinoid Research
- Treatment of Major Depression
- Pain Management and Opioid Use
- Dietary Effects on Health
National Institute on Drug Abuse
2021-2025
National Institutes of Health
2021-2025
Office of Extramural Research
2023-2024
University at Buffalo, State University of New York
2017-2022
Jacobs Institute
2019
4-Phosphoryloxy-N,N-dimethyltryptamine (psilocybin) is a naturally occurring tertiary amine found in many mushroom species. Psilocybin prodrug for 4-hydroxy-N,N-dimethyltryptamine (psilocin), which induces psychedelic effects via agonist activity at the serotonin (5-HT) 2A receptor (5-HT2A). Several other 4-position ring-substituted tryptamines are present psilocybin-containing mushrooms, including secondary 4-phosphoryloxy-N-methyltryptamine (baeocystin) and quaternary ammonium...
Primary metabolites of mushroom tryptamines, psilocybin and baeocystin (i.e., psilocin norpsilocin), exhibit potent agonist activity at the serotonin 2A receptor (5-HT2A) in vitro but differ their 5-HT2A-mediated effects vivo. In particular, produces centrally mediated psychedelic vivo, whereas norpsilocin, differing only by loss an N-methyl group, is devoid psychedelic-like effects. These observations suggest that secondary methylamine group norpsilocin impacts its central nervous system...
Abstract Identification of N,N-dimethylpentylone (DMP) in counterfeit “Ecstasy” and “Molly” tablets poses risk to public health due its adverse effects. Little information is available regarding the pharmacological activity or relevant blood tissue concentrations DMP, even less known about other structurally related beta-keto methylenedioxyamphetamine analogs on recreational drug markets, such as N-propyl butylone. Here, a novel toxicological assay utilizing liquid chromatography–tandem...
Analogues of 4-phosphoryloxy-
Serotonergic psychedelics induce the head twitch response (HTR) in mice, an index of serotonin (5-HT) 2A receptor (5-HT ) agonism and a behavioral proxy for psychedelic effects humans. Existing methods detecting HTRs include time-consuming visual scoring, invasive magnetometer-based approaches, analysis videos using semi-automated commercial software. Here, we present new automated approach quantifying open-source machine learning-based toolkits, DeepLabCut (DLC) Simple Behavioral Analysis...
Lisuride is a non-psychedelic serotonin (5-HT) 2A receptor (5-HT2A) agonist and analogue of the psychedelic lysergic acid diethylamide (LSD). also acts as an at 1A (5-HT1A), property known to counter effects. Here, we tested whether lisuride lacks activity due dual mechanism: (1) partial agonism 5-HT2A (2) potent 5-HT1A. The in vitro effects lisuride, LSD, related analogues on signaling were characterized by using miniGαq β-arrestin 2 recruitment assays. 5-HT1A- 5-HT2A-mediated LSD compared...
Synthetic cathinones are a class of new psychoactive substances that induce psychostimulant effects and pose risk for hospitalizations, overdose, death. At the present time, derivatives synthetic cathinone, methylone, being confiscated in nonmedical (i.e., recreational) drug markets worldwide. In particular, eutylone is newly emerging methylone analog possesses ethyl groups at α-carbon amine positions. Little information available about pharmacological eutylone, but based on its structure,...
Aeruginascin (4-phosphoryloxy-N,N,N-trimethyltryptammonium) is an analogue of psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine) that has been identified in several species psilocybin-containing mushrooms. Our team previously reported the synthesis, structural characterization, and biological activity putative metabolite aeruginascin (4-hydroxy-N,N,N-trimethyltryptammonium; 4-HO-TMT) its potential prodrug (4-acetoxy-N,N,N-trimethyltryptammonium; 4-AcO-TMT). Here, we report pharmacological...
Abstract Rationale The potent synthetic opioid fentanyl, and its analogs, continue to drive opioid-related overdoses. Although the pharmacology of fentanyl is well characterized, there little information about reinforcing effects clandestine analogs (FAs). Objectives Here, we compared FAs acetylfentanyl, butyrylfentanyl, cyclopropylfentanyl on drug self-administration in male female rats. These feature chemical modifications at carbonyl moiety scaffold. Methods Sprague-Dawley rats fitted...
Integrated in silico chemical clustering and melatonin receptor molecular modeling combined with vitro 2-[<sup>125</sup>I]-iodomelatonin competition binding were used to identify carbamate insecticides affinity for human 1 (hMT<sub>1</sub>) 2 (hMT<sub>2</sub>). Saturation kinetic studies revealed lead carbamates (carbaryl, fenobucarb, bendiocarb, carbofuran) be orthosteric ligands antagonist apparent efficacy at hMT<sub>1</sub> agonist hMT<sub>2</sub>. Furthermore, using quantitative...
Psychedelics are a class of drugs that produce unique subjective effects via agonist actions at the 5-hydroxytryptamine 2A receptor (5-HT2A). The 5-HT2A-mediated head twitch response (HTR) in rodents is used as reliable proxy for psychedelic drug activity humans, but existing methods measuring HTRs require surgery or time-consuming visual scoring. In present work, we validated simple noninvasive method quantitating using computer-based analysis experimental video recordings. Male C57BL/6J...