Understanding the complex pharmacology of cannabidiol: Mounting evidence suggests a common binding site with cholesterol.
Pharmacol Res
; 166: 105508, 2021 04.
Article
em En
| MEDLINE
| ID: mdl-33610721
ABSTRACT
Cannabidiol is claimed to bind to a large number of protein targets based on in vitro assays. This suggests opportunities for a wide range of therapeutic applications. On the other hand, the existence of phytochemical 'nuisance compounds' suggests some measure of caution - these compounds are capable of altering membrane biophysical properties and changing protein function without directly contacting a binding site. Like cannabidiol, cholesterol alters membrane properties, but it also binds directly to membrane proteins through abundant cholesterol recognition sites. We present the evidence that cannabidiol and cholesterol may bind to the same site on some proteins. As a starting point for further research, we also used blind docking to show that cannabidiol binds to a cholesterol binding site on the CB1 receptor. Elucidation of the mechanism(s) of action of cannabidiol will assist the prioritisation of in vitro hits across targets, improve the success rate of medicinal chemistry campaigns, and ultimately benefit patient populations by focusing resources on programs with the most translational potential.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Canabidiol
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Colesterol
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Receptor CB1 de Canabinoide
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Anticonvulsivantes
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article