Allosteric modulators in CNS disorders: review

Abstract

A variety of central nervous system disorders were treated using G protein-coupled receptors (GPCRs) modulators. The discovery of allosteric modulators of GPCRs offers novel treatments with added benefits compared to orthosteric site modulators of GPCRs. The target site for allosteric modulators is separate from the orthosteric site and is still able to modulate the receptor function. Allosteric modulators either potentiate or inhibit the receptor response, and provide much greater subtype selectivity those orthostatic agents for the same receptors. Experiments revealed Positive Allosteric Modulators show allosteric agonism when used in combination with an endogenous ligand. Allosteric modulators permit increased drug selectivity and demonstrate a significant decrease in adverse effects. Studies showed the potential of some allosteric modulators of GPCRs and AMPA receptors in multiple Central Nervous System disorders including Alzheimer's and Parkinson's disease.