Mini Reviews in Medicinal Chemistry - Volume 5, Issue 7, 2005

Cannabinoids have been predominantly considered as the substances responsible of the psychoactive properties of marijuana and other derivatives of Cannabis sativa. However, these compounds are now being also considered for their therapeutic potential, since the term “cannabinoid” includes much more compounds than those present in Cannabis sativa derivatives. Among them, there are numerous synthetic cannabinoids obt Read More

Since the discovery that cannabinoids exert biological actions through binding to specific receptors, signal mechanisms triggered by these receptors have been focus of extensive study. This review summarizes the current knowledge of the signalling events produced by cannabinoids from membrane receptors to downstream regulators. Two types of cannabinoid receptors have been identified to date: CB1 and CB2 bo Read More

The CB1 receptor is expressed in the central nervous system and numerous other tissues including heart, lung and uterus and has been recognized as an important therapeutic target for pain, appetite modulation, glaucoma, multiple sclerosis and other indications. An interesting feature of this GPCR is its ability to be activated by a number of structurally different classes of compounds, thus, raising the possibility of multiple activ Read More

The CB1 receptor is found principally in the central nervous system and is responsible for the overt physiological effects of cannabinoids. In contrast, the CB2 receptor is expressed primarily in the immune system and is responsible for few, if any, obvious behavioral effects. Although many cannabinoid receptor ligands show little, or at best modest, selectivity for either receptor, a number of synthetic compounds are k Read More

In absence of X ray crystal structures of G-protein coupled receptors (GPCRs)-ligand complexes, computer-aided molecular modeling together with site-directed mutagenesis studies become of great importance in order to provide in-silico predictions that facilitate the development of new ligands. In this context, the present review addresses the application of these strategies to the CB1 and CB2 cannabinoid receptors. The Read More

Novel pharmacological tools and the generation of null-mutants enabled the elucidation of the role of endocannabinoids in cognition and emotionality of rats and mice. Endocannabinoids seem to limit memory retention, to facilitate memory extinction and to ensure adequate coping with stressful situations. A selective potentiation of these actions may lead to novel pharmacotherapies for human anxiety disorders.

There is a growing amount of evidence suggesting that cannabinoids may be neuroprotective in CNS inflammatory conditions. Advances in the understanding of the physiology and pharmacology of the cannabinoid system have increased the interest of cannabinoids as potential therapeutic targets. Cannabinoid receptors and their endogenous ligands, the endocannabinoids, have been detected in cells of the immune system Read More

From library shaping to ADME-Tox prediction via virtual screening, computational chemistry is an integral component of Lead Generation. It provides a series of tools that help focusing on compounds with a balanced pharmacodynamic and ADME-Tox profile together with a high potential to optimize potency and selectivity.

Genetic alterations are responsible for all cancers. These mutations produce, in turn, alterations in key proteins of certain signaling pathways. Amongst the best known and studied alterations related to malignant transformations are those which occur in Ras protein and p53. In most cases mutations in Ras and p53 lead to the appearance of practically most malignant transformations. Mutated Ras genes exist in approximat Read More