| Indication | For use in the management of the manifestations of psychotic disorders and for the control of severe nausea and vomiting in adults. |
| Pharmacodynamics | 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. |
| Absorption | Absolute bioavailability is 40% following oral administration. |
| Volume of distribution | Not Available |
| Protein binding | Not Available |
| Metabolism | Hepatic. |
| Route of elimination | Perphenazine is extensively metabolized in the liver to a number of metabolites by sulfoxidation, hydroxylation, dealkylation, and glucuronidation. |
| Half life | 8-12 hours, but ranges up to 20 hours. |
| Clearance | Not Available |
| Toxicity | 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) |