Endocannabinoid Hydrolase Inhibitors: Potential Novel Anxiolytic Drugs.
Drug Des Devel Ther
; 18: 2143-2167, 2024.
Article
in En
| MEDLINE
| ID: mdl-38882045
ABSTRACT
Over the past decade, the idea of targeting the endocannabinoid system to treat anxiety disorders has received increasing attention. Previous studies focused more on developing cannabinoid receptor agonists or supplementing exogenous cannabinoids, which are prone to various adverse effects due to their strong pharmacological activity and poor receptor selectivity, limiting their application in clinical research. Endocannabinoid hydrolase inhibitors are considered to be the most promising development strategies for the treatment of anxiety disorders. More recent efforts have emphasized that inhibition of two major endogenous cannabinoid hydrolases, monoacylglycerol lipase (MAGL) and fatty acid amide hydrolase (FAAH), indirectly activates cannabinoid receptors by increasing endogenous cannabinoid levels in the synaptic gap, circumventing receptor desensitization resulting from direct enhancement of endogenous cannabinoid signaling. In this review, we comprehensively summarize the anxiolytic effects of MAGL and FAAH inhibitors and their potential pharmacological mechanisms, highlight reported novel inhibitors or natural products, and provide an outlook on future directions in this field.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Anti-Anxiety Agents
/
Endocannabinoids
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Enzyme Inhibitors
/
Amidohydrolases
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Monoacylglycerol Lipases
Limits:
Animals
/
Humans
Language:
En
Journal:
Drug Des Devel Ther
Year:
2024
Document type:
Article