Allosteric Modulators of Dopamine D 2 Receptors for Fine-Tuning of Dopaminergic Neurotransmission in CNS Diseases: Overview, Pharmacology, Structural Aspects and Synthesis.

Allosteric modulation of G protein-coupled receptors (GPCRs) is nowadays a hot topic in medicinal chemistry. Allosteric modulators, i.e., compounds which bind in a receptor site topologically distinct from orthosteric sites, exhibit a number of advantages. They are more selective, safer and display a ceiling effect which prevents overdosing. Allosteric modulators of dopamine D 2 receptor are potential drugs against a number of psychiatric and neurological diseases, such as schizophrenia and Parkinson's disease. In this review, an insightful summary of current research on D 2 receptor modulators is presented, ranging from their pharmacology and structural aspects of ligand-receptor interactions to their synthesis.