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Article
Open AccessStructural basis for activation of CB1 by an endocannabinoid analog
Endocannabinoids (eCBs) are endogenous ligands of the cannabinoid receptor 1 (CB1), a G protein-coupled receptor that regulates a number of therapeutically relevant physiological responses. Hence, understandin...
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Article
Synthon-based ligand discovery in virtual libraries of over 11 billion compounds
Structure-based virtual ligand screening is emerging as a key paradigm for early drug discovery owing to the availability of high-resolution target structures1–4 and ultra-large libraries of virtual compounds5,6....
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Article
Cannabinoid-induced lower lip retraction in rats
Lower lip retraction (LLR) in rats has been described as a distinctive effect of 5-HT1A agonists. In the course of evaluating behavioral effects of cannabinoid agonists in rats, LLR effects were evident following...
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Article
Inhibitor of Endocannabinoid Deactivation Protects Against In Vitro and In Vivo Neurotoxic Effects of Paraoxon
The anticholinesterase paraoxon (Pxn) is related to military nerve agents that increase acetylcholine levels, trigger seizures, and cause excitotoxic damage in the brain. In rat hippocampal slice cultures, hig...
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Article
Crystal structures of agonist-bound human cannabinoid receptor CB1
Crystal structures of the human cannabinoid receptor 1 (CB1) bound to the agonists AM11542 and AM841 reveal notable structural rearrangements upon receptor activation, and this flexibility may be a common feature...
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Article
Effects of fatty acid amide hydrolase (FAAH) inhibitors on working memory in rats
Manipulations of the endocannabinoid system could potentially produce therapeutic effects with minimal risk of adverse cannabis-like side effects. Inhibitors of fatty acid amide hydrolase (FAAH) increase endog...
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Article
Cannabinoid withdrawal in mice: inverse agonist vs neutral antagonist
Previous reports shows rimonabant’s inverse properties may be a limiting factor for treating cannabinoid dependence. To overcome this limitation, neutral antagonists were developed, to address mechanisms by wh...
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Article
New aminoadamantane derivatives with antiproliferative activity
1-Benzyl-2-aminoadamantanes 2a–c, conformationally constrained aminoadamantanes 3a, b and 4 and diaminoadamantanes derivatives 5a–c, 6a–c were synthesized and tested as antiproliferative agents. The in vitro biol...
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Article
The Interaction of Fatty Acid Amide Hydrolase (FAAH) Inhibitors with an Anandamide Carrier Protein Using 19 F-NMR
It has been reported that the endocannabinoid anandamide (AEA) binds to a class of fatty acid-binding proteins and serum albumin which can serve as carrier proteins and potentiate the cellular uptake of AEA an...
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Article
AM2389, a high-affinity, in vivo potent CB1-receptor-selective cannabinergic ligand as evidenced by drug discrimination in rats and hypothermia testing in mice
The endocannabinoid signaling system (ECS) has been targeted for develo** novel therapeutics since ECS dysfunction has been implicated in various pathologies. Current focus is on chemical modifications of th...
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Article
A New Generation Fatty Acid Amide Hydrolase Inhibitor Protects Against Kainate-Induced Excitotoxicity
Endocannabinoids, including anandamide (AEA), have been implicated in neuroprotective on-demand responses. Related to such a response to injury, an excitotoxic kainic acid (KA) injection (i.p.) was found to in...
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Protocol
Methods for the Synthesis of Cannabinergic Ligands
During the last decade, numerous cannabinergic ligands with high affinity and selectivity profiles for cannabinoid receptors (CB1 and CB2) emerged from rigorously pursued structure-activity relationship studies. ...
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Article
The role of halogen substitution in classical cannabinoids: A CB1 pharmacophore model
The presence of halogens within the classical cannabinoid structure leads to large variations in the compounds' potencies and affinities for the CB1 receptors. To explore the structure activity relationships w...
