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Comparison of anandamide transport in FAAH wild-type and knockout neurons: evidence for contributions by both FAAH and the CB1 receptor to anandamide uptake.
TLDR
The results indicate that the protein-dependent uptake of AEA is largely mediated by known constituents of the endocannabinoid system (FAAH and the CB1 receptor), although a partial contribution of an additional UCM707-sensitive protein is also suggested.
Assignment of endogenous substrates to enzymes by global metabolite profiling.
TLDR
A general strategy for identifying endogenous substrates of enzymes by untargeted liquid chromatography-mass spectrometry (LC-MS) analysis of tissue metabolomes from wild-type and enzyme-inactivated organisms is described to discover several brain lipids regulated by the mammalian enzyme fatty acid amide hydrolase in vivo.
Pharmacological activity of fatty acid amides is regulated, but not mediated, by fatty acid amide hydrolase in vivo.
TLDR
The results indicate that FAAH is a key regulator, but not mediator of FAA activity in vivo, and suggest that FAAs represent a family of signaling lipids that, despite sharing similar chemical structures and a common pathway for catabolism, produce their behavioral effects through distinct receptor systems in vivo.
Functional disassociation of the central and peripheral fatty acid amide signaling systems.
TLDR
The data suggest that the central and peripheral FAA signaling systems regulate discrete behavioral processes and may be targeted for distinct therapeutic gain.
Increased Seizure Susceptibility and Proconvulsant Activity of Anandamide in Mice Lacking Fatty Acid Amide Hydrolase
TLDR
It is shown that the administration of anandamide dramatically augments the severity of chemically induced seizures in FAAH (−/−) mice but not in wild-type mice, and the disinhibitory actions of endocannabinoids observed in hippocampal slices in vitro may also occur in vivo.
Predicting opioid receptor binding affinity of pharmacologically unclassified designer substances using molecular docking
TLDR
The strong correlation between the binding scores and the experimental binding affinities suggests that this approach can be used to accurately predict the binding strength of newly identified fentanyl analogs at the mu receptor and may assist in the temporary scheduling of those substances that pose a risk to public safety.
Assessing the Structural and Pharmacological Similarity of Newly Identified Drugs of Abuse to Controlled Substances Using Public Health Assessment via Structural Evaluation
The US Food and Drug Administration's Center for Drug Evaluation and Research (CDER) developed an investigational Public Health Assessment via Structural Evaluation (PHASE) methodology to provide a
Evaluating kratom alkaloids using PHASE
TLDR
The Public Health Assessment via Structural Evaluation (PHASE) protocol is applied to generate in silico binding profiles for 25 kratom alkaloids to facilitate the risk evaluation of kratom and demonstrates the ability of PHASE to identify potential safety signals and provide a tool for prioritizing experimental evaluation of high-risk compounds.
A Novel Cholinergic Action of Alcohol and the Development of Tolerance to That Effect in Caenorhabditis elegans
TLDR
Data suggest that cholinergic signaling through a specific α-subunit-containing nAChR is involved in ethanol-induced excitation and that tolerance to this ethanol effect is modulated by Na+/K+ ATPase function.
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