RESERPINE

Clinical safety rating: safe

Animal studies have demonstrated safety

How it works

Reserpine inhibits the vesicular monoamine transporter (VMAT2), preventing uptake of norepinephrine, dopamine, and serotonin into presynaptic vesicles, leading to depletion of monoamine neurotransmitters in nerve terminals.

What the body does with it

Metabolism	Extensively metabolized in the liver via hydrolysis and conjugation; no single major CYP enzyme identified.
Excretion	Primarily metabolized in the liver; less than 1% excreted unchanged in urine; elimination mainly via feces as metabolites after biliary excretion.
Half-life	Terminal elimination half-life is approximately 50-100 hours (mean ~50 hours in hypertensive patients; up to 100 hours in some individuals). The long half-life allows for once-daily dosing but also leads to prolonged washout and delayed onset/offset of pharmacodynamic effects.
Protein binding	Approximately 96% bound to plasma proteins, primarily albumin.
Volume of Distribution	Very large volume of distribution, approximately 9-10 L/kg, indicating extensive tissue binding and accumulation in adipose tissue and organs such as the brain.
Bioavailability	Oral bioavailability is approximately 50% due to extensive first-pass metabolism in the liver; highly variable inter- and intraindividually.
Onset of Action	Oral: 3-6 days for antihypertensive effect; maximum effect may require 3-6 weeks. Intramuscular: Not commonly used; onset of sedation within 2-3 hours.
Duration of Action	Oral: Antihypertensive effect persists for 1-6 weeks after discontinuation due to irreversible binding to catecholamine storage vesicles. Duration of action significantly exceeds elimination half-life. Sedative effects may last 4-6 hours after a single dose.

Classification & Brands

Dosing & administration

0.1-0.25 mg orally once daily. Initial dose 0.5 mg daily for 1-2 weeks, then reduce to maintenance.

Dosage form	TABLET
Renal impairment	No specific adjustment recommended; use with caution in severe renal impairment (CrCl <30 mL/min) due to increased risk of adverse effects.
Liver impairment	Child-Pugh A: no adjustment. Child-Pugh B: reduce dose by 50%. Child-Pugh C: avoid use.
Pediatric use	0.02 mg/kg/day orally in 1-2 divided doses; maximum 0.25 mg/day. Not recommended for children <6 years.
Geriatric use	Initiate at 0.05 mg orally once daily; increase slowly. Increased risk of hypotension, sedation, and depression. Avoid use if history of depression.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

MAOIs can cause excitability and hypertension Can cause depression and suicidal ideation.

Breastfeeding	Reserpine is excreted in breast milk; M/P ratio not well established. Potential for significant infant exposure causing adverse effects (drowsiness, diarrhea, nasal congestion). Breastfeeding is generally not recommended during therapy.
Teratogenic Risk	Reserpine crosses the placenta. First trimester: Animal studies show teratogenicity (cleft palate, skeletal anomalies); human data limited but avoid. Second/third trimesters: Associated with neonatal effects (respiratory depression, hypothermia, bradycardia, nasal congestion) due to catecholamine depletion. Risk of fetal harm cannot be excluded.

Warnings & precautions

■ FDA Black Box Warning

No FDA black box warning.

Side Effect Profile

Common Effects	Depression
Serious Effects

Absolute Contraindications

["History of depression","Active peptic ulcer or ulcerative colitis","Pheochromocytoma","Electroconvulsive therapy (ECT)","Hypersensitivity to reserpine"]

Clinical Precautions

Precautions

["Risk of depression, especially in patients with history","Activation of peptic ulcer","Bradycardia and arrhythmias","Extrapyramidal symptoms","Nasal congestion","Galactorrhea"]

Clinical Tips & Counseling

Drug interactions

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