Alpha-2A antagonist
Alpha-2A adrenergic receptor antagonist
- Releases the presynaptic brake on norepinephrine release
- If BBB-crossing: ↑ noradrenergic (and downstream serotonergic) tone
- Can raise arousal and blood pressure unless paired with alpha-1 antagonism
- Antagonist of α2A autoreceptor → sympatho-facilitatory (↑ NE tone) → pro-arousal 5-HT and DA
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; known for weight gain.
- Mitragynine — The main alkaloid of kratom; a 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.
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