scholarly journals Probing the CB1 Cannabinoid Receptor Binding Pocket with AM6538, a High-Affinity Irreversible Antagonist

2019 ◽  
Vol 96 (5) ◽  
pp. 619-628
Author(s):  
Robert B. Laprairie ◽  
Kiran Vemuri ◽  
Edward L. Stahl ◽  
Anisha Korde ◽  
Jo-Hao Ho ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Cannabinoid Receptor ◽  
Binding Pocket ◽  
High Affinity ◽  
Cb1 Cannabinoid Receptor

scholarly journals The Spicy Story of Cannabimimetic Indoles

Molecules ◽  
2021 ◽  
Vol 26 (20) ◽  
pp. 6190
Author(s):  
Allyn C. Howlett ◽  
Brian F. Thomas ◽  
John W. Huffman
Keyword(s):  
Electrostatic Interactions ◽  
Cannabinoid Receptor ◽  
Binding Pocket ◽  
Herbal Products ◽  
The Public ◽  
Aromatic Stacking ◽  
Cb1 Cannabinoid Receptor ◽  
Colchicine Binding Site ◽  
Consumer Safety ◽  
G Protein Coupled

The Sterling Research Group identified pravadoline as an aminoalkylindole (AAI) non-steroidal anti-inflammatory pain reliever. As drug design progressed, the ability of AAI analogs to block prostaglandin synthesis diminished, and antinociceptive activity was found to result from action at the CB1 cannabinoid receptor, a G-protein-coupled receptor (GPCR) abundant in the brain. Several laboratories applied computational chemistry methods to ultimately conclude that AAI and cannabinoid ligands could overlap within a common binding pocket but that WIN55212-2 primarily utilized steric interactions via aromatic stacking, whereas cannabinoid ligands required some electrostatic interactions, particularly involving the CB1 helix-3 lysine. The Huffman laboratory identified strategies to establish CB2 receptor selectivity among cannabimimetic indoles to avoid their CB1-related adverse effects, thereby stimulating preclinical studies to explore their use as anti-hyperalgesic and anti-allodynic pharmacotherapies. Some AAI analogs activate novel GPCRs referred to as “Alkyl Indole” receptors, and some AAI analogs act at the colchicine-binding site on microtubules. The AAI compounds having the greatest potency to interact with the CB1 receptor have found their way into the market as “Spice” or “K2”. The sale of these alleged “herbal products” evades FDA consumer protections for proper labeling and safety as a medicine, as well as DEA scheduling as compounds having no currently accepted medical use and a high potential for abuse. The distribution to the public of potent alkyl indole synthetic cannabimimetic chemicals without regard for consumer safety contrasts with the adherence to regulatory requirements for demonstration of safety that are routinely observed by ethical pharmaceutical companies that market medicines.

scholarly journals Metabolism, CB1 cannabinoid receptor binding and in vivo activity of synthetic cannabinoid 5F-AKB48: Implications for toxicity

2020 ◽  
Vol 195 ◽  
pp. 172949 ◽  
Author(s):  
Anna Pinson ◽  
Azure L. Yarbrough ◽  
John M. Bush ◽  
Christian V. Cabanlong ◽  
Amal Shoeib ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Cannabinoid Receptor ◽  
Synthetic Cannabinoid ◽  
Cb1 Cannabinoid Receptor

Falcarinol (Panaxynol) is a CB1 cannabinoid receptor antagonist and induces pro-allergic effects in skin

Planta Medica ◽  
2009 ◽  
Vol 75 (09) ◽  
Author(s):  
J Gertsch ◽  
M Leonti ◽  
L Casu ◽  
F Cottiglia ◽  
S Raduner ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Cannabinoid Receptor ◽  
Cb1 Cannabinoid Receptor

Is the Rigidity of SARS-CoV-2 Spike Receptor-Binding Motif the Hallmark for Its Enhanced Infectivity and Pathogenesis?

2020 ◽  
Author(s):  
Angelo Spinello ◽  
Andrea Saltalamacchia ◽  
Alessandra Magistrato
Keyword(s):  
Health Economic ◽  
Global Health ◽  
Receptor Binding ◽  
Binding Motif ◽  
Spike Glycoprotein ◽  
High Affinity ◽  
Global Pandemic ◽  
Medical Countermeasures ◽  
High Infectivity ◽  
Human Receptor

<p>The latest outbreak of a new pathogenic coronavirus (SARS-CoV-2) is provoking a global health, economic and societal crisis. All-atom simulations enabled us to uncover the key molecular traits underlying the high affinity of SARS-CoV-2 spike glycoprotein towards its human receptor, providing a rationale to its high infectivity. Harnessing this knowledge can boost developing effective medical countermeasures to fight the current global pandemic.</p>

scholarly journals Tricyclic Pyrazole-Based Compounds as Useful Scaffolds for Cannabinoid CB1/CB2 Receptor Interaction

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2126
Author(s):  
Battistina Asproni ◽  
Gabriele Murineddu ◽  
Paola Corona ◽  
Gérard A. Pinna
Keyword(s):  
Neuropathic Pain ◽  
Cannabinoid Receptor ◽  
Receptor Interaction ◽  
Pharmacological Properties ◽  
Cb2 Receptor ◽  
Antiemetic Effect ◽  
High Affinity ◽  
Cb1 Antagonist ◽  
Cb2 Receptors ◽  
Sar Study

Cannabinoids comprise different classes of compounds, which aroused interest in recent years because of their several pharmacological properties. Such properties include analgesic activity, bodyweight reduction, the antiemetic effect, the reduction of intraocular pressure and many others, which appear correlated to the affinity of cannabinoids towards CB1 and/or CB2 receptors. Within the search aiming to identify novel chemical scaffolds for cannabinoid receptor interaction, the CB1 antagonist/inverse agonist pyrazole-based derivative rimonabant has been modified, giving rise to several tricyclic pyrazole-based compounds, most of which endowed of high affinity and selectivity for CB1 or CB2 receptors. The aim of this review is to present the synthesis and summarize the SAR study of such tricyclic pyrazole-based compounds, evidencing, for some derivatives, their potential in the treatment of neuropathic pain, obesity or in the management of glaucoma.

Sign in / Sign up

Export Citation Format

Share Document