Alpha-2 receptor agonists activate inhibitory alpha-2 receptors in the CNS or peripheral tissues. Central agents reduce sympathetic outflow despite being adrenergic agonists.

Alpha-2 receptors couple to Gi, reducing cyclic AMP and norepinephrine release. Central brainstem activation decreases sympathetic discharge; spinal and supraspinal effects contribute to sedation and analgesia.

Clonidine, guanfacine, methyldopa, dexmedetomidine, brimonidine, apraclonidine and lofexidine are important examples.

Uses include hypertension, ADHD, selected withdrawal syndromes, glaucoma, perioperative or ICU sedation, analgesic adjunct use and pregnancy-associated hypertension with methyldopa where appropriate.

Sedation, dry mouth, bradycardia, hypotension and constipation may occur. Abrupt withdrawal of clonidine can cause rebound sympathetic activity and severe hypertension.

Taper chronic clonidine rather than stopping abruptly. Use caution with conduction disease, hypotension, severe bradycardia and concomitant sedatives; methyldopa has distinct risks including haemolysis and liver injury.