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Review
. 2009 Apr;21(2):122-33.
doi: 10.1080/09540260902782778.

Pharmacotherapeutic modulation of the endocannabinoid signalling system in psychiatric disorders: drug-discovery strategies

David R Janero  1 , Subramanian K Vadivel, Alexandros Makriyannis
Affiliations
Review

Pharmacotherapeutic modulation of the endocannabinoid signalling system in psychiatric disorders: drug-discovery strategies

David R Janero et al. Int Rev Psychiatry. 2009 Apr.

Abstract

Medicinal chemistry has produced small-molecule agents with drug-like character that potently and safely modulate the activity of discrete endocannabinoid system components as potential treatments for medical disorders, including various psychiatric conditions. Two cannabinoid (CB) receptors (CB1 and CB2) currently represent prime endocannabinoid-system therapeutic targets for ligands that either mimic endocannabinoid signalling processes and/or potentiate endocannabinoid-system activity (agonists) or attenuate pathologically heightened endocannabinoid-system transmission (antagonists). Two endocannabinoid deactivating enzymes, fatty acid amide hydrolase (FAAH) and soluble monoacylglycerol lipase (MGL), are increasingly prominent targets for inhibitors that indirectly potentiate endocannabinoid-system signalling. Continued profiling of drug candidates in relevant disease models, identification of additional cannabinoid-related therapeutic targets, and validation of new pharmacological modes of endocannabinoid system modulation will undoubtedly invite further translational efforts in the cannabinoid field for treating psychiatric disorders and other medical conditions.

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Conflict of interest statement

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Figures

Figure 1
Figure 1
Structures of the principal phytocannabinoids.
Figure 2
Figure 2
Structures of synthetic CB1/CB2-receptor agonists.
Figure 3
Figure 3
Structures of synthetic selective CB2-receptor agonists.
Figure 4
Figure 4
Structures of synthetic selective CB1-receptor agonists.
Figure 5
Figure 5
Structures of synthetic selective CB1-receptor antagonists/inverse agonists.
Figure 6
Figure 6
Structures of synthetic selective CB2-receptor antagonists/inverse agonists.
Figure 7
Figure 7
Structures of the principal endocannabinoids.
Figure 8
Figure 8
Structures of FAAH (AM374, URB597, LY2183240), MGL (LY2183240, NAM) and endocannabinoid transport (AM404) inhibitors.
See this image and copyright information in PMC

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