A5037492481- Psychedelics and Drug Studies
- Neurotransmitter Receptor Influence on Behavior
- Chemical synthesis and alkaloids
- Receptor Mechanisms and Signaling
- Pharmacological Receptor Mechanisms and Effects
- Adenosine and Purinergic Signaling
- Forensic Toxicology and Drug Analysis
- RNA Interference and Gene Delivery
- Radical Photochemical Reactions
- Advanced biosensing and bioanalysis techniques
- Neuroscience and Neuropharmacology Research
- Cholinesterase and Neurodegenerative Diseases
- Photoreceptor and optogenetics research
- Pancreatic function and diabetes
- Analytical Chemistry and Chromatography
- Lipid Membrane Structure and Behavior
- Photochromic and Fluorescence Chemistry
- Nicotinic Acetylcholine Receptors Study
- Advanced Drug Delivery Systems
- Biochemical Analysis and Sensing Techniques
- Cannabis and Cannabinoid Research
- Immunotherapy and Immune Responses
- Olfactory and Sensory Function Studies
- Computational Drug Discovery Methods
- Migraine and Headache Studies
Ghent University
2017-2025
Ghent University Hospital
2024
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...
Abstract 2-Benzylbenzimidazole ‘nitazene’ opioids are presenting a growing threat to public health. Although various nitazenes were previously studied, systematic comparisons of the effects different structural modifications 2-benzylbenzimidazole core structure on μ-opioid receptor (MOR) activity limited. Here, we assessed in vitro structure–activity relationships 9 uncharacterized alongside known analogues. Specifically, focused MOR activation by ‘ring’ substituted analogues (i.e., N...
The delivery of RNA across biological barriers can be achieved by encapsulation in lipid nanoparticles (LNPs). Cationic amphiphilic drugs (CADs) are pharmacologically diverse compounds with ionizable lipid-like features. In this work, we applied CADs as a fifth component state-of-the-art LNPs via microfluidic mixing. Improved cytosolic both siRNA and mRNA was partly replacing the cholesterol fraction CADs. could cross mucus layer mucus-producing air-liquid interface model human primary...
The serotonin 7 receptor (5-HT7R) regulates various processes in the central nervous system, including mood, learning, and circadian rhythm control, among others. Receptor activation can lead to of Gαs protein a subsequent increase intracellular cyclic adenosine monophosphate (cAMP). interaction with inverse agonists results decrease basal cAMP levels therefore downstream effect reduced neuronal excitability neurotransmission. Recently, pellotine (1a), Lophophora alkaloid, was unexpectedly...
The serotonin 2A receptor (5-HT2AR) is the most abundant excitatory in brain and primary target for serotonergic psychedelics. Despite its importance, receptor's mechanism of action structure-activity relationships are not fully understood. experimental 5-HT2AR structures have identified a hydrophobic tunnel lateral to orthosteric site, situated between transmembrane helices 4 5. Here, we examined this implications agonist pharmacology. characteristics key roles Phe2345x39 Gly2385x43 were...
The serotonin 2A receptor (5-HT
Classical psychedelics are a group of hallucinogens which trigger non-ordinary states consciousness through activation the 5-HT2A receptor (5-HT2A R) in brain. However, exact mechanism how R agonism alters perception remains elusive. When studying signaling, tools work at same spatiotemporal resolution as exceptionally useful. To create such tool, we designed set photoswitchable ligands based on classical psychedelic N,N-dimethyltryptamine (DMT). By incorporation DMT-indole ring into system,...
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...
2-Arylethynyl (N)-methanocarba adenosine 5′-methylamides are selective A3 receptor (AR) agonists containing a preestablished receptor-preferred pseudoribose conformation. Here, we compare analogues having bulky 2-substitution, either or lacking an ethynyl spacer between adenine and cyclic group. 2-Aryl compounds 9–11, 13, 14, 19, 22, 23, 27, 29, 31, 34, spacer, had human (h) A3AR Ki values of 2–30 nM, others displayed lower affinity. Mouse (m) affinity varied, with 2-arylethynyl higher than...
Serotonergic psychedelics are described to have activation of the serotonin 2A receptor (5-HT2A) as their main pharmacological action. Despite relevance, molecular mechanisms underlying psychedelic effects induced by certain 5-HT2A agonists remain elusive. One proposed hypotheses is occurrence biased agonism, defined preferential signaling pathways over others. This study comparatively monitored efficiency a diverse panel 4-position-substituted (and N-benzyl-derived) phenylalkylamines induce...
Serotonergic psychedelics are defined as compounds having serotonin 2A receptor (5-HT2AR) activation an important pharmacological mechanism. These include the phenylalkylamine class, containing substances with e.g. 2C-X structures (phenethylamines) or their N-methoxybenzyl analogues (NBOMes). Besides abuse potential, increasingly recognized for therapeutic benefits. However, many remain incompletely characterized, even concerning structure-activity relationships. Here, five positional...
Abstract Background Since late 2019, fortification of ‘regular’ cannabis plant material with synthetic cannabinoid receptor agonists (SCRAs) has become a notable phenomenon on the drug market. As many SCRAs pose higher health risk than genuine cannabis, recognizing SCRA-adulterated is important from harm reduction perspective. However, this not always an easy task as adulterated may only be distinguished by dedicated, often expensive and time-consuming analytical techniques. In addition,...
Classic or serotonergic hallucinogens comprise the third largest number of reported new psychoactive substances (NPS), according to United Nations Office on Drugs and Crime. While being structurally very divergent, they share activation serotonin 2A receptor (5-HT2AR), a G protein-coupled receptor, as their main pharmacological mechanism. Here, we report development 5-HT2AR bioassay, which monitors β-arrestin2 recruitment via split-luciferase system, measure activation. Possible applications...
Quality of life is often reduced in patients with sleep-wake disorders. Insomnia commonly treated benzodiazepines, despite their well-known side effects. Pellotine (
Serotonergic psychedelics, substances exerting their pharmacological action through activation of the serotonin 2A receptor (5-HT2AR), have continuously comprised a substantial fraction over 1000 reported New Psychoactive Substances (NPS) so far. Within this category, N-benzyl derived phenethylamines, such as NBOMes and NBFs, shown to be particular relevance. As these remain incompletely characterized, study aimed at synthesizing positional isomers 25H-NBF, with two methoxy groups placed on...
The A
<b>Abstract ID 93958</b> <b>Poster Board 481</b> A<sub>3</sub> adenosine receptor (AR) agonists are being developed for the treatment of autoimmune inflammatory diseases, chronic pain and cancer. A<sub>3</sub>AR not limited by cardiovascular side effects observed with other (A<sub>1</sub>and A<sub>2A</sub>) that were in clinical trials. 2-Arylethynyl (North)-methanocarba adenosines have been explored as highly selective agonists, which is largely a function pseudoribose (bicyclic fused...