Alpha-2A agonist
Alpha-2A adrenergic receptor agonist
- If BBB-crossing:
- Presynaptic autoreceptor → ↓ locus coeruleus firing
- Improves prefrontal attention/impulse control
- ↓ sympathetic tone → ↓ BP, sedation
- Abrupt stop → rebound HTN
- Relieves opioid-withdrawal adrenergic symptoms
- Improves prefrontal cortex tuning by reducing NE “noise”→ better attention/impulse control
- Sedation at higher doses
- Analgesia via spinal nociceptive suppression
- Dry mouth
- Decreased sweating (helps hyperhidrosis)
- Peripheral vasoconstriction
- ↓ aqueous humor → ↓ intraocular pressure (ophthalmic)
- ↓ aqueous humor and ↑ uveoscleral outflow
- Less vascular impact than α2A (minimal BP lowering)
- Dry mouth +
Drugs with this mechanism (17)
- Brimonidine — Alpha-2 agonist for glaucoma and rosacea redness.
- Clonidine — Central alpha-2 agonist for hypertension, ADHD and withdrawal; sedation and rebound.
- Clonidine ER — Extended-release central alpha-2 agonist for ADHD; sedation and rebound hypertension limit it.
- Dexmedetomidine — Alpha-2 agonist for cooperative sedation without respiratory depression.
- Dexmedetomidine sublingual — Sublingual dexmedetomidine film for acute agitation in schizophrenia or bipolar disorder.
- Guanabenz — Central alpha-2 agonist antihypertensive, now rare.
- Guanfacine — Alpha-2A agonist; non-stimulant ADHD agent, also for tics; sedation, hypotension.
- Guanfacine ER — Long-acting alpha-2A agonist for ADHD; less sedating than clonidine but still hypotensive.
- Lofexidine — Alpha-2 agonist for opioid-withdrawal symptoms.
- α-methylnorepinephrine — Active methyldopa metabolite; central alpha-2 agonism reduces sympathetic outflow and blood pressure.
- Moxonidine — Central imidazoline I1 agonist for hypertension in some countries; dry mouth and dizziness, with avoidance in heart failure.
- Norepinephrine — Endogenous catecholamine; the first-line vasopressor for shock.
- Clonidine ER suspension — Extended-release clonidine liquid for ADHD; sedation and rebound hypertension shape use.
- Oxymetazoline — Topical alpha agonist decongestant; rebound congestion with overuse.
- Rilmenidine — Central imidazoline I1 agonist used for hypertension outside the U.S.; reduces sympathetic activity, with dry mouth and dizziness.
- Tizanidine — Short-acting alpha-2 agonist for spasticity; hypotension and CYP1A2 interactions.
- Xylazine — Veterinary alpha-2 sedative ("tranq") now adulterating street fentanyl.
Self-check
- What salivary adverse effect is associated with alpha-2A agonism?
Dry mouth. - What aqueous-humor change explains ophthalmic alpha-2A agonism lowering pressure?
Decreased production.
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