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Phenothiazines
medication Under reviewPhenothiazines are a large class of nitrogen- and sulfur-containing tricyclic compounds best known as first‑generation or “typical” antipsychotic drugs, including agents such as chlorpromazine, fluphenazine, perphenazine, and promethazine. They act primarily as dopamine D2 receptor antagonists in mesolimbic and other dopaminergic pathways, which reduces positive psychotic symptoms such as hallucinations and delusions. Many members of the class also show antagonism at histamine H1, muscarinic acetylcholine, and alpha-adrenergic receptors, producing prominent sedative, anticholinergic, and cardiovascular effects. Clinically, phenothiazines are used mainly as prescription medications for schizophrenia, other psychotic disorders, acute mania, and severe agitation, and some members are used at lower doses for nausea, vomiting, intractable hiccups, acute migraine, and perioperative sedation. They are not nutritional supplements and are not appropriate for self-directed use in healthy individuals. In addition to their established psychiatric uses, there is emerging research exploring phenothiazine derivatives as potential anticancer or antiviral agents, but these applications remain investigational and are not part of routine clinical care.
Research summary
Human research on phenothiazines in healthy subjects mainly involves pharmacokinetics, safety, and their use as short‑term antiemetic or sedative agents around surgery or procedures. At therapeutic doses, they reliably produce central nervous system effects such as sedation and impaired psychomotor performance, along with anticholinergic symptoms like dry mouth and constipation. These effects can appear even in healthy volunteers and are dose‑dependent. Serious adverse reactions, including extrapyramidal symptoms, QT prolongation, and neuroleptic malignant syndrome, are primarily characterized in patient populations but represent known risks for any exposed individual. Modern research interest increasingly focuses on repurposing phenothiazines or designing novel derivatives for oncology and infectious diseases based on mechanisms such as calmodulin inhibition, interference with cellular signaling, and disruption of lysosomal function. Current anticancer work is largely preclinical, with a few early‑phase clinical trials where phenothiazines or derivatives are combined with standard care in patients, not healthy volunteers. Overall, there is no evidence base supporting phenothiazines as a health-promoting supplement in healthy people; instead, they are potent prescription drugs with a substantial side‑effect and interaction profile.
Reported Side Effects
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Electroencephalographic and psychomotor effects of chlorpromazine and risperidone relative to placebo in normal healthy volunteers.
Simpson GM, Jurich J
The effects of prochlorperazine on psychomotor performance and mood in normal subjects
Shaw JA, Wittenborn JR
Effects of single therapeutic doses of promethazine, fexofenadine and olopatadine on psychomotor function and histamine-induced wheal- and flare-responses: a randomized double-blind, placebo-controlled study in healthy volunteers.
Kay GG, Harris AG
No reports yet
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The effects of prochlorperazine on psychomotor performance and mood in normal subjects
Shaw JA, Wittenborn JR
Effects of single therapeutic doses of promethazine, fexofenadine and olopatadine on psychomotor function and histamine-induced wheal- and flare-responses: a randomized double-blind, placebo-controlled study in healthy volunteers.
Kay GG, Harris AG
Electroencephalographic and psychomotor effects of chlorpromazine and risperidone relative to placebo in normal healthy volunteers.
Simpson GM, Jurich J
No reports yet
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Add Phenothiazines to your stack to report effects
Effects of single therapeutic doses of promethazine, fexofenadine and olopatadine on psychomotor function and histamine-induced wheal- and flare-responses: a randomized double-blind, placebo-controlled study in healthy volunteers.
Kay GG, Harris AG
Electroencephalographic and psychomotor effects of chlorpromazine and risperidone relative to placebo in normal healthy volunteers.
Simpson GM, Jurich J
No reports yet
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Cardiovascular and autonomic effects of chlorpromazine in normal man
Janssen PA, Jageneau AH
Electroencephalographic and psychomotor effects of chlorpromazine and risperidone relative to placebo in normal healthy volunteers.
Simpson GM, Jurich J
No reports yet
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Cardiovascular and autonomic effects of chlorpromazine in normal man
Janssen PA, Jageneau AH
No reports yet
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Add Phenothiazines to your stack to report effects
Effects of single therapeutic doses of promethazine, fexofenadine and olopatadine on psychomotor function and histamine-induced wheal- and flare-responses: a randomized double-blind, placebo-controlled study in healthy volunteers.
Kay GG, Harris AG
No reports yet
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Add Phenothiazines to your stack to report effects
Extrapyramidal reactions following single doses of prochlorperazine in normal subjects
Bowers MB Jr, Ajlouny MA
Research (5 studies)
Effects of single therapeutic doses of promethazine, fexofenadine and olopatadine on psychomotor function and histamine-induced wheal- and flare-responses: a randomized double-blind, placebo-controlled study in healthy volunteers.
Kay GG, Harris AG
Electroencephalographic and psychomotor effects of chlorpromazine and risperidone relative to placebo in normal healthy volunteers.
Simpson GM, Jurich J
The effects of prochlorperazine on psychomotor performance and mood in normal subjects
Shaw JA, Wittenborn JR
Extrapyramidal reactions following single doses of prochlorperazine in normal subjects
Bowers MB Jr, Ajlouny MA
Cardiovascular and autonomic effects of chlorpromazine in normal man
Janssen PA, Jageneau AH
Community updates
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