Current Medicinal Chemistry - Volume 17, Issue 14, 2010

The plant Cannabis sativa produces ∼80 terpeno-phenol compounds, termed “phytocannabinoids”, among which Δ9- tetrahydrocannabinol (THC) is the most psychotropic component [1]. THC binds to specific G-protein-coupled receptors (GPCRs), named type-1 (CB1) and type-2 (CB2) cannabinoid receptors, that are also activated by endogenous ligands called “endocannabinoids” (eCBs). Among these lipid substances Read More

In this review we describe recent advances in the chemistry of novel CB1/CB2 agonists, CB1 antagonists, selective CB2 agonists, fatty acid amide hydrolase inibitors, monoglyceride (MGL) and diglyceride (DAGL) inhibitors and cannabinoid-type agonists and antagonists of non CB1/CB2 receptors. In view of recent interest in the activities of fatty acid amides of amino acids (N-acyl amino acids) a list of this type of compou Read More

It is widely accepted that non-endogenous compounds that target CB1 and/or CB2 receptors possess therapeutic potential for the clinical management of an ever growing number of disorders. Just a few of these disorders are already treated with Δ9-tetrahydrocannabinol or nabilone, both CB1/CB2 receptor agonists, and there is now considerable interest in expanding the clinical applications of such agonists and also in Read More

CB1 receptors are G-protein coupled receptors (GPCRs) abundant in neurons, in which they modulate neurotransmission. The CB1 receptor influence on memory and learning is well recognized, and disease states associated with CB1 receptors are observed in addiction disorders, motor dysfunction, schizophrenia, and in bipolar, depression, and anxiety disorders. Beyond the brain, CB1 receptors also function in liver and Read More

Marijuana has been used for thousands of years to affect human health. Dissecting the peripheral effects from the central psychotropic effects has revealed a complex interplay between cannabinoids, endocannabinoids and their receptors. This review examines recent advances in understanding the expression, regulation and utilization of the CB2 receptor. Here we highlight the molecular aspects of the CB2 recept Read More

In the last decade, accumulated evidence highlighted that GPR55 might be activated by several classical cannabinoid ligands, making this orphan receptor the main candidate to be considered as the “third” cannabinoid receptor. The investigation of its pharmacology has often provided divergent and more intricate results, that have complicated the understanding of the physiological role of GPR55. Nevertheless, the pate Read More

In the late 1990's, a series of experiments carried out independently in two laboratories led to establish an important connection between the function of the endocannabinoids, which, as exemplified in this special issue, is per se very complex and ubiquitous in animals, and that of the transient receptor potential (TRP) channels, a large family of plasma membrane cation channels involved in several mammalian and no Read More

Peroxisome proliferator-activated receptors (PPARs) have long been known as mediators of several physiological functions, among which the best characterized are lipid metabolism, energy balance and anti-inflammation. Their rather large and promiscuous ligand binding site has been recently discovered to accommodate, among a plethora of lipid molecules and metabolic intermediates, endocannabinoids and their co Read More

The cannabinoid CB1 and CB2 receptors are Class A G protein-coupled receptors (GPCRs). While many Class A GPCRs have endogenous ligands that are hydrophilic cations (e.g., the serotonin and dopamine receptors), the cannabinoid receptors have neutral, highly lipophilic ligands derived from the fatty acid, arachidonic acid. The most well-studied of these are N-arachidonoylethanolamine (anandamide, AEA) and sn-2-arachidon Read More

Cellular signaling is regulated by several biochemical reactions, whose dynamics depends on changes in the fluxes of specific ligands through the containment barriers that are the biological membranes. The regulation of this complex dynamic equilibrium is mainly due to the activity of border proteins, that must be able to interact simultaneously with the lipid bilayer and the extracellular milieu. Endocannabinoid receptors, that Read More