Definition
An antipsychotic phenothiazine derivative with actions and uses similar to those of CHLORPROMAZINE.
Description
An antipsychotic phenothiazine derivative with actions and uses similar to those of chlorpromazine. [PubChem]
Top Gene Interactions
Related Pathways
General Information
- 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.
Toxicity
- 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 Aldehyde oxidase |
12825922 20853847 17145705 10991983 6149136 |
|
Calmodulin 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. |
17016423 1515867 16661928 7828655 9616188 23675993 16910628 10688273 11873706 9333110 17139284 11409178 10516112 12366848 8689810 17455212 7508675 |
Perphenazine Interacts with Diseases
Disease | Inference Score | References/Inference Genes |
Hypogonadism | 16.44 |
|
Hyperprolactinemia | 13.51 |
|
Male infertility | 10.85 |
|
Infertility, Female | 9.5 |
|
Leydig Cell Tumor | 9.19 |
|
Bradycardia | 8.19 |
|
Pituitary Neoplasms | 7.7 |
|
Amenorrhea | 7.58 |
|
Cocaine dependence | 6.72 |
|
Alcohol dependence | 6.39 |
|
Follicle-stimulating hormone deficiency, isolated | 5.79 |
|
Short QT Syndrome 1 | 5.77 |
|
Amphetamine-Related Disorders | 5.44 | |
Basal Ganglia Diseases | 5.38 |
|
Tachycardia | 5.21 |
|
Lateral Medullary Syndrome | 5.1 |
|
Long Qt Syndrome 2 | 5.08 |
|
Catalepsy | 5.01 |
|
Parkinsonian Disorders | 4.96 |
|
Myoclonic dystonia | 4.91 |
|