Allosteric modulators of α4β2 nicotinic acetylcholine receptors: a new direction for antidepressant drug discovery

摘要: Allosteric modulation of ligand-gated ion channels has been intensively studied in the past three decades and is now an established strategy to control receptor function numerous disease states. sites on GABA(A) are targets for widely prescribed drugs that used a variety pathophysiological states including insomnia epilepsy. Modulators might be especially valuable receptors which design selective orthosteric proven difficult due safety issues (e.g., α4β2 nicotinic acetylcholine have several advantages over ligands. influence action endogenous agonist but generally no effect their own unoccupied receptor. Moreover, higher subtype selectivity exerted by modulators effects depend simultaneous presence help overcome problems preventing over-dosage compared with administration drugs.