RESERPINE
Clinical safety rating: safe
Animal studies have demonstrated safety
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.
| 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. |
| Molecular Weight | 608.68 |
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. |
| 1st trimester | Avoid; crosses placenta; associated with increased risk of congenital malformations, especially CNS and cardiovascular defects. |
| 2nd trimester | Avoid; may cause fetal bradycardia, hypotonia, and respiratory depression due to catecholamine depletion. |
| 3rd trimester | Avoid; near term may cause neonatal respiratory depression, bradycardia, hypothermia, and poor feeding. |
Clinical note
MAOIs can cause excitability and hypertension Can cause depression and suicidal ideation.
| Placental transfer | Reserpine crosses the placenta readily, achieving fetal plasma concentrations similar to maternal levels. It binds extensively to melanin-containing tissues and accumulates in fetal brain and eyes. |
| Breastfeeding | Reserpine is excreted into breast milk in small amounts; however, significant dose may accumulate in infants. Cases of neonatal bradycardia and cyanosis reported. The long half-life (50-100 hours) poses risk of accumulation. Use while breastfeeding is generally not recommended; alternative agents preferred. |
■ FDA Black Box Warning
No FDA black box warning.
| Common Effects | Depression |
| Serious Effects |
Known hypersensitivity to reserpine or other rauwolfia alkaloidsHistory of mental depression (especially if severe or requiring electroconvulsive therapy)Active peptic ulcerUlcerative colitisPatients with pheochromocytoma
| Precautions | Risk of depression, especially in patients with history, Activation of peptic ulcer, Bradycardia and arrhythmias, Extrapyramidal symptoms, Nasal congestion, Galactorrhea |
| Food/Dietary | Avoid tyramine-rich foods (aged cheeses, cured meats, fermented products) if also taking MAOIs. No specific food interactions reported with reserpine alone, but advise a low-sodium diet to complement antihypertensive effect. |
Loading safety data…
| Lactation Rating | L5 |
| 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. |
| Fetal Monitoring | Monitor maternal blood pressure and heart rate regularly. Assess fetal heart rate and growth by ultrasound due to potential for intrauterine growth restriction. Neonatal observation for respiratory depression, bradycardia, and nasal stuffiness at delivery. |
| Fertility Effects | Reserpine may inhibit ovulation due to prolactin elevation (dopamine depletion). In males, can cause decreased libido, impotence, and gynecomastia. Reversible upon discontinuation. |
| Clinical Pearls | Reserpine is an irreversible inhibitor of the vesicular monoamine transporter (VMAT), depleting catecholamines and serotonin from nerve terminals. Onset of action is slow (weeks) and effect persists after discontinuation due to irreversible binding. It is rarely used today due to high rates of depression (15-20%) and other adverse effects. Avoid in patients with history of depression, peptic ulcer disease, or pheochromocytoma. Monitor for signs of depression, bradycardia, and nasal congestion. Concomitant use with MAOIs may cause hypertensive crisis. |
| Patient Advice | Take this medication exactly as prescribed, usually once daily; it may take several weeks to see full effect. · Do not stop taking this medication suddenly without consulting your doctor, as this may cause a rapid increase in blood pressure. · You may experience drowsiness, dizziness, or nasal congestion; avoid driving or operating machinery until you know how this medication affects you. · Report any signs of depression, such as persistent sadness, loss of interest, or changes in sleep or appetite, to your healthcare provider immediately. · Avoid alcohol and over-the-counter cold or allergy medications containing decongestants, as they may interfere with this drug. |