2617 Haloperidol A phenyl-piperidinyl-butyrophenone that is used primarily to treat schizophrenia and other psychoses. It is also used in schizoaffective disorder, delusional disorders, ballism, and tourette syndrome (a drug of choice) and occasionally as adjunctive therapy in mental retardation and the chorea of huntington disease. It is a potent antiemetic and is used in the treatment of intractable hiccups. (From AMA Drug Evaluations Annual, 1994, p279) 52-86-8 3559 C21H23ClFNO2 375.140130 White to faintly yellowish, amorphous or micro-crystalline powder (A638). 151.5°C 14 mg/L (at 25°C) Inhalation, Oral (60%) The precise mechanism whereby the therapeutic effects of haloperidol are produced is not known, but the drug appears to depress the CNS at the subcortical level of the brain, midbrain, and brain stem reticular formation. Haloperidol seems to inhibit the ascending reticular activating system of the brain stem (possibly through the caudate nucleus), thereby interrupting the impulse between the diencephalon and the cortex. The drug may antagonize the actions of glutamic acid within the extrapyramidal system, and inhibitions of catecholamine receptors may also contribute to haloperidol's mechanism of action. Haloperidol may also inhibit the reuptake of various neurotransmitters in the midbrain, and appears to have a strong central antidopaminergic and weak central anticholinergic activity. The drug produces catalepsy and inhibits spontaneous motor activity and conditioned avoidance behaviours in animals. The exact mechanism of antiemetic action of haloperidol has also not been fully determined, but the drug has been shown to directly affect the chemoreceptor trigger zone (CTZ) through the blocking of dopamine receptors in the CTZ. 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 LD50: 128 mg/kg (Oral, Rat) LD50: 71 mg/kg (Oral, Mouse) LD50: 90 mg/kg (Oral, Dog) LD50: 165 mg/kg (Oral, Rat) No indication of carcinogenicity to humans (not listed by IARC). 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. 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). LD₅₀=165 mg/kg (rats, oral) 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) 2009-07-05T03:35:09Z 2014-12-24T20:25:43Z Cytochrome P450 1A2 (CYP1A2) (P05177) (A308) Cytochrome P450 2D6 (CYP2D6) (P10635) (A308). Haloperidol C01814 5613 Haloperidol DB00502 true Cytochrome P450 1A2 (P05177) Cytochrome P450 2D6 (P10635) (A308) OC1(CCN(CCCC(=O)C2=CC=C(F)C=C2)CC1)C1=CC=C(Cl)C=C1 C21H23ClFNO2 InChI=1S/C21H23ClFNO2/c22-18-7-5-17(6-8-18)21(26)11-14-24(15-12-21)13-1-2-20(25)16-3-9-19(23)10-4-16/h3-10,26H,1-2,11-15H2 InChIKey=LNEPOXFFQSENCJ-UHFFFAOYSA-N 375.864 375.140134897 Exogenous Solid 4.3 HMDB14645 CHEMBL54 3438 <p><a href="http://www.drugsyn.org/Haloperidol.htm">DrugSyn.org</a></p>