Molecular pharmacology of alpha2-adrenoceptor agonists

The three α2-adrenergic receptor subtypes mediate many of the physiological actions of the catecholamines noradrenaline and adrenaline and are important drug targets in cardiovascular, neuropsychiatric and anaesthetic clinical practice. The three receptors share many common structural and functional properties, but they mediate different physiological and pharmacological effects due to their different tissue distribution. The α2Asubtype is responsible for most of the major pharmacological effects ascribed to α2-adrenoceptor agonists (the central regulation of blood pressure and sympathetic nerve activity, nociceptive processing, and the control of alertness, attention and vigilance); the α2Bsubtype mediates vasoconstriction; and the α2Csubtype is involved in sensorimotor integration. Small differences in receptor structure may pave the way for the development of subtype-selective α2-adrenergic agents with an improved therapeutic and safety profile.