Reserpine
Adrenergic neuron blockers
Adrenergic neuron blockers
A rauwolfia alkaloid that empties the noradrenaline stores of nerves. The first effective antihypertensive, now rarely used.
Quick facts
- Group
- Adrenergic neuron blockers
- Target
- Vesicular monoamine transporter 2 (VMAT2)
- Used for
- High blood pressure
- Key effects
- Sedation and poor concentration · Nasal stuffiness
- Monitor
- Mood and signs · Blood pressure and heart rate
- ATC
- C02AA02
No doses: the clinician sets them by the current guideline.
Mechanism of action
The figure shows reserpine bound to human VMAT2, the transporter that loads monoamines into vesicles.
Reserpine binds tightly, almost irreversibly, to VMAT2 on storage vesicles in central and peripheral neurons. Vesicles can no longer take up and store noradrenaline and dopamine (and serotonin); the amines leak into the cytoplasm and are broken down by MAO. Little transmitter is released, causing a 'pharmacological sympathectomy': cardiac output and vascular resistance fall. Recovery needs new vesicles, which takes days to weeks.
- Binds VMAT2 on storage vesicles almost irreversibly
- Vesicles cannot store noradrenaline, dopamine or serotonin
- Amines leak out and are broken down by MAO
- Sympathetic tone falls; heart rate and blood pressure drop
Indications
- High blood pressure (now rarely, usually in low doses with a diuretic) Arterial hypertension →
- Severe agitation in mental disorders (historical use)
Adverse effects
Common
- Sedation and poor concentration
- Nasal stuffiness
- Slow heart rate and dizziness
- Diarrhoea, upset stomach, dry mouth
- Nightmares
- Reduced sexual function
Contraindications
- Current or past depression
- Active peptic ulcer or ulcerative colitis
- Electroconvulsive therapy
- Hypersensitivity to rauwolfia alkaloids
Key interactions
- Indirect-acting sympathomimetics (ephedrine, amphetamine-like drugs)
- Lose much of their effect, because they act by releasing the stores reserpine has emptied.
- Alcohol and other CNS depressants
- More sedation and dizziness.
- Other antihypertensives
- Additive fall in blood pressure.
What is monitored
- Mood and signs of depression at every visit
- Blood pressure and heart rate
- Gastrointestinal symptoms (ulcer)
Administration and safety
- Oral tablet, usually once a day.
- Effect builds over weeks and persists after stopping; a sudden stop can let pressure rise.
- Tell the surgical and anaesthesia team before an operation.
Pregnancy and breastfeeding
Its safety in pregnancy is not well established, and better-studied antihypertensives are used instead.
Nursing care
- Before: screen for a history of depression or peptic ulcer.
- During: ask about mood, sleep and nightmares; report low mood promptly.
- Check pulse and blood pressure; teach to rise slowly.
- Teach that alcohol increases drowsiness.
Pharmacokinetics
- Absorption
- Oral.
- Metabolism
- Free drug is fully metabolized; little parent drug is excreted unchanged.
- Onset and duration
- Slow: full effect takes weeks, and the effect outlasts the drug for days to weeks because of irreversible binding.
Test yourself
Think of the answer, then tap the question to see it.
Why can reserpine cause depression?
It also empties brain stores of noradrenaline, dopamine and serotonin by blocking VMAT2.
Why does reserpine's effect last long after it is stopped?
It binds VMAT2 almost irreversibly; recovery needs new vesicles, which takes days to weeks.
Which two adverse effects of reserpine come from unopposed parasympathetic tone?
Nasal stuffiness and slow heart rate (also more gastric acid and diarrhoea).
A patient on reserpine gets ephedrine for hypotension and barely responds. Why?
Ephedrine works mostly by releasing stored noradrenaline, which reserpine has depleted.
Connections
← Back to the class: Adrenergic neuron blockers
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: Reserpine: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2024); Human VMAT2 in complex with reserpine (RCSB Protein Data Bank, 2023); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).
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Representative model, for educational purposes only.