Alpha-2A antagonist
Alpha-2A adrenergic receptor antagonist
- Releases the presynaptic brake on norepinephrine release
- If BBB-crossing: ↑ noradrenergic (and downstream serotonergic) tone
- Antagonist of α2A autoreceptor → sympatho-facilitatory (↑ NE tone) → pro-arousal 5-HT and DA
- Can raise arousal and blood pressure unless paired with alpha-1 antagonism
Drugs with this mechanism (7)
- 1-PP — Buspirone metabolite; alpha-2 antagonism that adds noradrenergic activation the parent does not have.
- Mianserin — Tetracyclic antidepressant; forerunner of mirtazapine (not US).
- Mirtazapine — Sedating, appetite-stimulating noradrenergic/serotonergic agent; weight gain.
- Mitragynine — Main kratom alkaloid; mu-opioid partial agonist.
- Phenoxybenzamine — Irreversible alpha blocker for pheochromocytoma.
- Phentolamine — Reversible alpha blocker for pheochromocytoma and vasopressor extravasation.
- Yohimbine — Alpha-2 antagonist supplement; raises noradrenaline and anxiety.
Self-check
- How does alpha-2A blockade affect norepinephrine release?
Removes presynaptic inhibition, increasing release. - What coexisting action can counter the BP rise from alpha-2A blockade?
Alpha-1 antagonism.
All mechanisms · Open Alpha-2A antagonist in the interactive console ↗