Alpha agonists activate alpha-adrenergic receptors. Peripheral alpha-1 agonists mainly constrict vascular or mucosal smooth muscle, whereas central alpha-2 agonists reduce sympathetic outflow.

Alpha-1 receptors couple to Gq and increase intracellular calcium. Alpha-2 receptors couple to Gi and inhibit adenylyl cyclase and transmitter release; central activation reduces sympathetic tone.

Phenylephrine, midodrine and oxymetazoline are alpha-1-predominant agents. Clonidine, methyldopa, guanfacine, dexmedetomidine and brimonidine are alpha-2-predominant agents.

Uses include hypotension, orthostatic hypotension, nasal or ocular decongestion, mydriasis, hypertension, ADHD, glaucoma, ICU or procedural sedation and selected withdrawal states.

Alpha-1 agonists can cause hypertension, reflex bradycardia, ischaemia and urinary retention. Alpha-2 agonists can cause sedation, dry mouth, bradycardia and hypotension; abrupt clonidine withdrawal can cause rebound hypertension.

Use cautiously in severe hypertension, coronary or peripheral vascular disease and urinary retention. Topical decongestants should not be overused because rebound congestion can occur.