Résumé
The two main neurotransmitters, glutamate and GABA, as well as calcium ions, sweet taste molecules and some pheromones, act on class-C G-protein-coupled receptors (GPCRs). These natural ligands bind within the large extracellular domain of these receptors. Recently, both negative and positive allosteric modulators have been identified for many of these receptors. These compounds bind in the heptahelical domain and possess several specific properties that make them good candidates for multiple therapeutic and industrial applications.
Michael Spedding – Institut de Recherches Internationales Servier, France
Class-C GPCRs have become an increasingly important target class for new therapies, particularly in areas such as pain, anxiety, neurodegenerative disorders and as antispasmodics, but also potentially for the treatment of hyperthyroidism and osteoporosis. Both positive and negative allosteric modulators have been identified against many targets in this class and can be particularly therapeutically active because they tend to be highly selective towards the targeted receptors. Furthermore, they often have useful attributes such as the ability to cross the blood–brain barrier whilst having fewer side effects than agonists. The binding sites of many of these allosteric modulators have now been identified and radioligands developed which should make the future identification of new compounds acting at these sites much easier.