Chlorpromazine — Thorazine — was the first effective antipsychotic, introduced in 1952. Its discovery transformed asylum psychiatry: patients who had been institutionalized for years could be discharged. The "tranquilizer revolution" began with chlorpromazine, and modern deinstitutionalization is partly its legacy. Today the drug is rarely used as an antipsychotic, but the story of chlorpromazine teaches you the receptor-profile principle better than any other agent.
- Class
- Low-potency first-generation antipsychotic
- Mechanism
- D2 antagonism plus substantial H1, M1, alpha-1 antagonism
- Typical dose
- 100-800 mg/day
- Half-life
- ~30 hours
- FDA indications
- Schizophrenia, severe behavioral problems, intractable hiccups (off-label), nausea/vomiting
- Key adverse effects
- Sedation (prominent), orthostatic hypotension, anticholinergic effects, weight gain, photosensitivity, less EPS than high-potency FGAs
Black box: Increased mortality in elderly patients with dementia-related psychosis
Historically the first effective antipsychotic (1950s) — defined the era. Modern use limited but still found for severe behavioral problems, intractable hiccups, and adjunctive nausea control. Sedation is the dominant clinical feature.
Chlorpromazine is a low-potency FGA. The receptor profile is multi-target: D2 antagonism for the antipsychotic effect, plus substantial H1 antagonism (sedation), M1 anticholinergic activity, and alpha-1 antagonism (orthostasis). The breadth is what produces the clinical character.
The H1 effect makes chlorpromazine sedating — heavily so at antipsychotic doses, which is much of the reason the drug was originally hailed as a "tranquilizer." The M1 effect causes anticholinergic burden — dry mouth, constipation, blurred vision, urinary retention, cognitive impairment, which is a substantial concern in elderly patients. The alpha-1 effect produces orthostatic hypotension. Together these effects explain why chlorpromazine has a different feel than haloperidol despite both being D2 antagonists.
Chlorpromazine is the prototype low-potency FGA — its loose D2 blockade is accompanied by heavy off-target receptor activity that defines its sedating, hypotensive profile.
Mechanism note: Low-potency FGAs trade EPS for sedation, hypotension, and anticholinergic burden — the inverse profile of high-potency agents. Chlorpromazine is the archetype of that trade-off.
Counterintuitively, the M1 anticholinergic activity actually reduces EPS compared to haloperidol. Anticholinergic agents treat EPS; chlorpromazine has anticholinergic activity built in. So while overall side effects are higher with chlorpromazine, EPS specifically is lower.
- Cost
- Generic: ~$15-40/month.
- Generic status
- Generic for decades.
- Formulary typical
- Tier 1 generic. Limited modern use.
- Access friction
- Some pharmacies don't stock; advance order may be needed.
Prescriber tip: Rarely used today. For intractable hiccups, sometimes still the answer — ensure pharmacy can fill before sending the prescription.
Modern niches are narrow but specific. Severe agitation when other options are exhausted. Intractable hiccups — chlorpromazine is uniquely effective and remains on some hospital protocols for this rare indication. Adjunctive nausea control in oncology. Patients who have responded historically. New starts are rare; the drug shows up mostly as legacy treatment in chronic patients or specific niche uses.