Top Gene Interactions
- 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.
- Uses/Sources: For use in the management of the manifestations of psychotic disorders and for the control of severe nausea and vomiting in adults.
- Symptoms: Symptoms of overdose include stupor or coma, and children may have convulsive seizures. Signs of arousal may not occur for 48 hours.
- Treatment: Treatment is symptomatic and supportive. Induction of emesis is not recommended because of the possibility of a seizure, CNS depression, or dystonic reaction of the head or neck and subsequent aspiration. Gastric lavage (after intubation, if the patient is unconscious) and administration of activated charcoal together with a laxative should be considered. There is no specific antidote. Standard measures (oxygen, intravenous fluids, corticosteroids) should be used to manage circulatory shock or metabolic acidosis. An open airway and adequate fluid intake should be maintained. Body temperature should be regulated. Hypothermia is expected, but severe hyperthermia may occur and must be treated vigorously. An electrocardiogram should be taken and close monitoring of cardiac function instituted if there is any sign of abnormality. 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. (L1712)
- Route of Exposure: Absolute bioavailability is 40% following oral administration.
- Carcinogenicity: No indication of carcinogenicity to humans (not listed by IARC).
- Toxicity: LD50:318 mg/kg (Oral, Rat) (A308) LD50: 64 mg/kg (Intraperitoneal, Mouse) (A308)
Mechanism of Action
|Target Name||Mechanism of Action||References|
Muscarinic acetylcholine receptor M2
5-hydroxytryptamine receptor 2C
Alpha-2A adrenergic receptor
5-hydroxytryptamine receptor 7
Histamine H1 receptor
NADPH oxidase 1
Ubiquitin-conjugating enzyme E2 N
Alpha-1A adrenergic receptor
D(2) dopamine receptor
D(1A) dopamine receptor
Cytochrome P450 2D6
|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.||
Perphenazine Interacts with Diseases
|Disease||Inference Score||References/Inference Genes|
|Leydig Cell Tumor||9.19||
|Follicle-stimulating hormone deficiency, isolated||5.79||
|Short QT Syndrome 1||5.77||
|Basal Ganglia Diseases||5.38||
|Lateral Medullary Syndrome||5.1||
|Long Qt Syndrome 2||5.08||