Reserpine

Reserpine is an indole alkaloid obtained from the roots of Rauwolfia serpentina, commonly known as Indian snakeroot. It was isolated in the 1950s and later developed as one of the first oral antihypertensive medications, playing a significant role in the history of cardiovascular and psychiatric pharmacotherapy.

Mechanism of action: Reserpine blocks the vesicular monoamine transporter 2 (VMAT2) in adrenergic and serotonergic neurons, preventing uptake of norepinephrine, dopamine, and serotonin into synaptic vesicles. This depletes neurotransmitter stores, reducing sympathetic tone and lowering blood pressure. Central monoamine depletion also produces sedative and depressive effects.

Clinical use: Historically used for hypertension; also used in psychiatry for certain psychotic disorders in the 1950s and 1960s. Due to risk of severe depression and suicidality, its use declined and it is now rarely prescribed in most settings. It may still be encountered in very limited circumstances or for educational purposes; derivative compounds in research may alter risk profiles.

Adverse effects: Depression, apathy, irritability, mood changes; sedation; fatigue; insomnia; bradycardia and orthostatic hypotension; nasal stuffiness; gastrointestinal symptoms. It is contraindicated in individuals with a history of major depressive disorder or suicidal ideation.

Pharmacology and status: Administered orally; long duration of action due to irreversible VMAT2 inhibition and slow turnover of stores; lipophilic and capable of crossing the blood-brain barrier; extensive hepatic metabolism with renal or fecal excretion. It is noted for its historical impact and its role as a model of monoamine depletion therapy.