Adrenergic alpha-2 Receptor Antagonists
Overview
Overview
Alpha-2 receptor antagonists block inhibitory alpha-2 receptors and can increase norepinephrine release. They have limited routine cardiovascular use compared with alpha-1 antagonists.
Classification
Classification
Yohimbine is a relatively selective alpha-2 antagonist. Mirtazapine blocks central alpha-2 receptors as part of a broader antidepressant receptor profile, while atipamezole is mainly used in veterinary medicine.
Mechanism of action
Mechanism of action
Presynaptic alpha-2 blockade removes negative feedback on norepinephrine release, increasing sympathetic and central noradrenergic activity. Additional receptor effects determine each drug’s overall clinical profile.
Important members
Important members
Yohimbine is the classic pharmacological example. Mirtazapine has alpha-2-antagonist activity but is classified clinically as an antidepressant rather than a selective adrenergic drug.
Clinical uses
Clinical uses
Selective alpha-2 antagonists have little routine medical use. Yohimbine has historical use in erectile dysfunction but limited evidence and important safety concerns; mirtazapine is used for depressive disorders.
Adverse effects
Adverse effects
Anxiety, agitation, hypertension, tachycardia, tremor and insomnia can occur with yohimbine. Mirtazapine more commonly causes sedation, increased appetite and weight gain because of its broader receptor profile.
Contraindications and precautions
Contraindications and precautions
Avoid stimulant-like alpha-2 antagonism in uncontrolled hypertension, arrhythmia, severe anxiety or with interacting sympathomimetic drugs. Unregulated yohimbe products have uncertain dose and purity.
References
- National Institute of Diabetes and Digestive and Kidney Diseases. Yohimbine. NCBI Bookshelf. Updated 2020. SOURCE:NCBI:YOHIMBINE:2020
- Nachawati D, Patel JB. Alpha-Blockers. NCBI Bookshelf. Updated 2025. SOURCE:NCBI:ALPHA_BLOCKERS:2025