Definition
Description
Top Gene Interactions
Related Pathways
General Information
- Metabolism: Haloperidol is well absorbed from the gastrointestinal tract but first-pass hepatic metabolism decreases oral bioavailability to 40 to 75%. Serum concentration peaks 0.5 to 4 hours after an oral dose. Following administration of haloperidol, the drug is distributed mainly into the liver, with lower concentrations being distributed into the brain, lung, kidneys, spleen, and heart. Although the exact metabolic fate has not been clearly established, it appears that haloperidol is principally metabolized in the liver. The drug appears to be metabolized principally by oxidative N-dealkylation of the piperidine nitrogen to form fluorophenylcarbonic acids and piperidine metabolites (which appear to be inactive), and by reduction of the butyrophenone carbonyl to the carbinol, forming hydroxyhaloperidol. Limited data suggest that the reduced metabolite, hydroxyhaloperidol, has some pharmacologic activity, although its activity appears to be less than that of haloperidol. Urinary metabolites include p-fluorophenaceturic acid, beta-p-fluorobenzoylpropionic acid, and several unidentified acids (A637, A566, A637). Half Life: 3 weeks
- Uses/Sources: For the management of psychotic disorders (eg. schizophrenia) and delirium, as well as to control tics and vocal utterances of Tourette's syndrome (Gilles de la Tourette's syndrome). Also used for the treatment of severe behavioural problems in children with disrubtive behaviour disorder or ADHD (attention-deficit hyperactivity disorder). Haloperidol has been used in the prevention and control of severe nausea and vomiting.
- Health Effects: Tachycardia, hypotension, and hypertension; Extrapyramidal Symptoms (EPS) such as akathisia, or dystonia; impaired liver function and/or jaundice have been reported. Maculopapular and acneiform skin reactions and isolated cases of photosensitivity and loss of hair.Laryngospasm, bronchospasm, cataracts, retinopathy and visual disturbances; lactation, breast engorgement, mastalgia, menstrual irregularities, gynecomastia, impotence, increased libido, hyperglycemia, hypoglycemia and hyponatremia (RxList, A308).
- Symptoms: LD50=165 mg/kg (rats, oral)
- Treatment: Since there is no specific antidote, treatment is primarily supportive. A patent airway must be established by use of an oropharyngeal airway or endotracheal tube or, in prolonged cases of coma, by tracheostomy. Respiratory depression may be counteracted by artificial respiration and mechanical respirators. Hypotension and circulatory collapse may be counteracted by use of intravenous fluids, plasma, or concentrated albumin, and vasopressor agents such as metaraminol, phenylephrine and norepinephrine. Epinephrine should not be used. In case of severe extrapyramidal reactions, anti-Parkinson medication should be administered. ECG and vital signs should be monitored especially for signs of Q-T prolongation or dysrhythmias and monitoring should continue until the ECG is normal. Severe arrhythmias should be treated with appropriate anti-arrhythmic measures. (L1712)
- Route of Exposure: Inhalation, Oral (60%)
Toxicity
- Carcinogenicity: No indication of carcinogenicity to humans (not listed by IARC).
- Toxicity: LD50: 128 mg/kg (Oral, Rat) LD50: 71 mg/kg (Oral, Mouse) LD50: 90 mg/kg (Oral, Dog) LD50: 165 mg/kg (Oral, Rat)
Mechanism of Action
Target Name | Mechanism of Action | References |
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Potassium voltage-gated channel subfamily H member 2 Peroxisome proliferator-activated receptor delta Muscarinic acetylcholine receptor M1 Muscarinic acetylcholine receptor M5 Multidrug resistance protein 1 5-hydroxytryptamine receptor 2A 5-hydroxytryptamine receptor 2C 5-hydroxytryptamine receptor 1A Nuclear receptor subfamily 1 group I member 2 Sodium-dependent serotonin transporter Alpha-2A adrenergic receptor Sodium-dependent dopamine transporter Sodium-dependent noradrenaline transporter Mu-type opioid receptor Synaptic vesicular amine transporter 5-hydroxytryptamine receptor 7 D(3) dopamine receptor D(4) dopamine receptor Histamine H1 receptor Sigma non-opioid intracellular receptor 1 Alpha-2C adrenergic receptor Solute carrier family 22 member 1 Melanin-concentrating hormone receptor 1 |
9536001 18448342 11052797 7990111 1648140 23611293 7699710 9822559 12873512 9622542 22677319 7912402 1469697 12729675 9406603 16140009 15324906 19496999 12477351 10377229 18831971 12190308 15911273 23403082 7520908 15745831 16983399 17145705 8831770 16140011 16123775 18788725 |
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Glutamate receptor ionotropic, NMDA 2B D(2) dopamine receptor D(1A) dopamine receptor |
The precise mechanism whereby the therapeutic effects of haloperidol are produced is not known. Its effect on the central nervous system is thought to be associated with the competitive blockade of postsynaptic dopamine D2 receptors in the mesolimbic dopaminergic system and an increased turnover rate of brain dopamine. |
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