Brands, Medical Use, Clinical Data
- Dopamine Antagonists
- Tablet (2, 4, 8, or 16 mg)
Brands / Synonyms
Apo-Perphenazine; Chlorperphenazine; Decentan; Emesinal; Etaperazin; Etaperazine; Ethaperazine; Etrafon-A; Etrafon-Forte; F-Mon; Fentazin; Fluphenazine; Perfenazina; Perfenazine; Perphenan; Perphenazin; Perphenazine; Perphenazine and Amitriptyline; Perphenazine and Amitriptyline Hcl; Pms Perphenazine; PZC; Thilatazin; Tranquisan; Trifaron; Trilafon; Trilafon Concentrate; Trilifan; Triphenot
For use in the management of the manifestations of psychotic disorders and for the control of severe nausea and vomiting in adults.
Perphenazine is a piperazinyl phenothiazine, acts on the central nervous system, and has a greater behavioral potency than other phenothiazine derivatives whose side chains do not contain a piperazine moiety. It is a member of a class of drugs called phenothiazines, which are dopamine D1/D2 receptor antagonists. Perphenazine is 10 to 15 times as potent as chlorpromazine; that means perphenazine is a highly potent antipsychotic. In equivalent doses it has approximately the same frequency and severity of early and late extrapypramidal side-effects compared to Haloperidol.
Mechanism of Action
Binds to the dopamine D1 and dopamine D2 receptors and inhibits their activity. The mechanism of the anti-emetic effect is due predominantly to blockage of the dopamine D2 neurotransmitter receptors in the chemoreceptor trigger zone and vomiting centre. Perphenazine also binds the alpha andrenergic receptor. This receptor's action is mediated by association with G proteins that activate a phosphatidylinositol-calcium second messenger system.
Absolute bioavailability is 40% following oral administration.
Symptoms of overdose include stupor or coma, and children may have convulsive seizures. Signs of arousal may not occur for 48 hours. Oral LD50=318 mg/kg (rat); IPR LD50=64 mg/kg (mouse)
Biotrnasformation / Drug Metabolism
An electrocardiogram should be taken and close monitoring of cardiac function instituted if there is any sign of
abnormality. Cardiac arrhythmias may be treated with neostigmine, pyridostigmine, or propranolol. Digitalis should be
considered for cardiac failure. Close monitoring of cardiac function is advisable for not less than five days.
Vasopressors such as norepinephrine may be used to treat hypotension, but epinephrine should NOT be used.
Anticonvulsants (an inhalation anesthetic, diazepam, or paraldehyde) are recommended for control of convulsions,
since perphenazine increases the central nervous system depressant action, but not the anticonvulsant action of
If acute parkinson-like symptoms result from perphenazine intoxication, benztropine mesylate or diphenhydramine
may be administered.
Central nervous system depression may be treated with nonconvulsant doses of CNS stimulants. Avoid stimulants that
may cause convulsions (e.g., picrotoxin and pentylenetetrazol).
Signs of arousal may not occur for 48 hours.
Dialysis is of no value because of low plasma concentrations of the drug.
Since overdosage is often deliberate, patients may attempt suicide by other means during the recovery phase.
Deaths by deliberate or accidental overdosage have occurred with this class of drugs.
Metabolism of a number of medications, including antipsychotics, antidepressants, b- blockers, and
antiarrhythmics, occurs through the cytochrome P450 2D6 isoenzyme (debrisoquine hydroxylase). Approximately 10% of
the Caucasian population has reduced activity of this enzyme, so-called poorî metabolizers. Among other
populations the prevalence is not known. Poor metabolizers demonstrate higher plasma concentrations of antipsychotic
drugs at usual doses, which may correlate with emergence of side effects. In one study of 45 elderly patients
suffering from dementia treated with perphenazine, the 5 patients who were prospectively identified as poor P450 2D6
metabolizers had reported significantly greater side effects during the first 10 days of treatment than the 40
extensive metabolizers, following which the groups tended to converge. Prospective phenotyping of elderly patients
prior to antipsychotic treatment may identify those at risk for adverse events.
The concomitant administration of other drugs that inhibit the activity of P450 2D6 may acutely increase plasma
concentrations of antipsychotics. Among these are tricyclic antidepressants and selective serotonin reuptake
inhibitors, e.g.fluoxetine, sertraline and paroxetine. When prescribing these drugs to patients already receiving
antipsychotic therapy, close monitoring is essential and dose reduction may become necessary to avoid toxicity. Lower
doses than usually prescribed for either the antipsychotic or the other drug may be required.