Alpha-1 receptor agonists preferentially stimulate postsynaptic alpha-1 receptors on vascular and other smooth muscle. Their dominant clinical effect is vasoconstriction.

Alpha-1 receptors couple through Gq to phospholipase C, inositol trisphosphate and increased intracellular calcium, producing smooth-muscle contraction.

Phenylephrine is a direct alpha-1 agonist; midodrine is a prodrug whose active metabolite is an alpha-1 agonist. Oxymetazoline is used topically and has alpha-receptor activity.

Phenylephrine is used for selected hypotensive states and as a mydriatic or decongestant. Midodrine is used for symptomatic orthostatic hypotension; topical agents reduce nasal or conjunctival congestion.

Hypertension, reflex bradycardia, headache, urinary retention, piloerection and tissue ischaemia can occur. Topical nasal overuse may cause rebound congestion.

Avoid or use caution in severe hypertension, significant coronary or peripheral vascular disease, urinary retention and patients at risk from reduced cardiac output. Supine hypertension is a key concern with midodrine.