Abstract | INTRODUCTION: Excessive abdominal obesity along with other risk factors results in the metabolic syndrome, which can lead to heart disease, Type-2 diabetes, and death. The endocannabinoid system (ECS) is composed of neutral lipids which signal through the G-protein coupled cannabinoid receptors CB1 and CB2. In abdominal obesity, the ECS is generally up-regulated in central and peripheral tissues and its blockade results in positive metabolic changes. Rimonabant ( SR141716) was the first selective CB1 inverse agonist/antagonist marketed for the treatment of obesity; however, psychiatric side effects, which may result from its actions in the brain or its inverse agonism, resulted in its removal from the market. Recently, key metabolic-modulatory roles for the ECS within peripheral tissues have come to light. Thus there has been significant effort put forth by several laboratories to develop either neutral or peripherally restricted CB1 antagonists. AREAS COVERED: In this review we shall provide an overview of the roles the ECS plays outside the brain in regulating metabolism, and highlight the latest advances in the development of neutral and/or peripherally restricted CB1 antagonists, and other state of the art strategies that minimize endocannabinoid overactivity. EXPERT OPINION:
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Authors | Cristoforo Silvestri, Vincenzo Di Marzo |
Journal | Expert opinion on investigational drugs
(Expert Opin Investig Drugs)
Vol. 21
Issue 9
Pg. 1309-22
(Sep 2012)
ISSN: 1744-7658 [Electronic] England |
PMID | 22780328
(Publication Type: Journal Article, Review)
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Chemical References |
- Cannabinoid Receptor Antagonists
- Endocannabinoids
- Piperidines
- Pyrazoles
- Receptor, Cannabinoid, CB1
- Rimonabant
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Topics |
- Animals
- Cannabinoid Receptor Antagonists
(pharmacology, therapeutic use)
- Drug Design
- Drug Inverse Agonism
- Endocannabinoids
(metabolism)
- Humans
- Metabolic Diseases
(drug therapy, physiopathology)
- Obesity, Abdominal
(complications)
- Piperidines
(pharmacology, therapeutic use)
- Pyrazoles
(pharmacology, therapeutic use)
- Receptor, Cannabinoid, CB1
(antagonists & inhibitors)
- Rimonabant
- Risk Factors
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