Details
Stereochemistry | UNKNOWN |
Molecular Formula | C21H23ClFNO2.C3H6O3 |
Molecular Weight | 465.942 |
Optical Activity | ( + / - ) |
Defined Stereocenters | 0 / 1 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CC(O)C(O)=O.OC1(CCN(CCCC(=O)C2=CC=C(F)C=C2)CC1)C3=CC=C(Cl)C=C3
InChI
InChIKey=BVUSNQJCSYDJJG-UHFFFAOYSA-N
InChI=1S/C21H23ClFNO2.C3H6O3/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;1-2(4)3(5)6/h3-10,26H,1-2,11-15H2;2,4H,1H3,(H,5,6)
Molecular Formula | C21H23ClFNO2 |
Molecular Weight | 375.864 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
Molecular Formula | C3H6O3 |
Molecular Weight | 90.0779 |
Charge | 0 |
Count |
|
Stereochemistry | RACEMIC |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 1 |
E/Z Centers | 0 |
Optical Activity | ( + / - ) |
DescriptionSources: http://www.drugbank.ca/drugs/DB00502Curator's Comment: Description was created based on several sources, including http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/015923s079lbl.pdf
Sources: http://www.drugbank.ca/drugs/DB00502
Curator's Comment: Description was created based on several sources, including http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/015923s079lbl.pdf
Haloperidol is 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. Haloperidol also exerts sedative and antiemetic activity. Haloperidol principal pharmacological effects are similar to those of piperazine-derivative phenothiazines. The drug has action at all levels of the central nervous system-primarily at subcortical levels-as well as on multiple organ systems. Haloperidol has strong antiadrenergic and weaker peripheral anticholinergic activity; ganglionic blocking action is relatively slight. It also possesses slight antihistaminic and antiserotonin activity. 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 marketed under the trade name Haldol among others.
CNS Activity
Originator
Sources: https://www.ncbi.nlm.nih.gov/pubmed/16433054
Curator's Comment: Haloperidol was synthesized on the 11th of February 1958 at the Janssen Laboratories, in Belgium.
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL219 Sources: https://www.ncbi.nlm.nih.gov/pubmed/14611858 |
17.0 nM [EC50] | ||
Target ID: CHEMBL217 Sources: http://www.drugbank.ca/drugs/DB00502 |
|||
Target ID: CHEMBL224 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7520908 |
53.0 nM [EC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | HALDOL Approved UseHALDOL (haloperidol) is indicated for use in the treatment of schizophrenia. HALDOL is indicated for the control of tics and vocal utterances of Tourette’s Disorder. Launch Date1986 |
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Primary | HALDOL Approved UseHALDOL (haloperidol) is indicated for use in the treatment of schizophrenia. HALDOL is indicated for the control of tics and vocal utterances of Tourette’s Disorder. Launch Date1986 |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
moderate [Ki 7.2 uM] | ||||
no [IC50 >10 uM] | ||||
no [IC50 >10 uM] | ||||
no [IC50 >133 uM] | ||||
no [IC50 >133 uM] | ||||
no [IC50 >133 uM] | ||||
no [IC50 >30 uM] | ||||
no [IC50 >50 uM] | ||||
no | ||||
yes [Activation 31.6228 uM] | ||||
yes [IC50 10.7 uM] | ||||
yes [IC50 141.9 uM] | ||||
yes [IC50 2.87 uM] | ||||
yes [IC50 25.3 uM] | ||||
yes [IC50 25.4 uM] | ||||
yes [IC50 3.6 uM] | ||||
yes [IC50 4.69 uM] | ||||
yes [IC50 8.2 uM] | ||||
yes | ||||
yes | ||||
yes |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
likely [Km 33 uM] | ||||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/015923s093s098,018701s071s076lbl.pdf#page=8 Page: (Label) 8, 27 |
major | |||
major | ||||
major | yes (co-administration study) Comment: Coadministration of CYP2D6 inhibitors (chlorpromazine, promethazine, quinidine, paroxetine, sertraline, venlafaxine) increased Haloperidol plasma concentrations. Page: (Label) 9, 28 |
|||
major | yes (co-administration study) Comment: Coadministration of Rifampicin (strong CYP3A4 inducer) decreased plasma Haloperidol levels by a mean of 70%. Page: (Label) 9, 28 |
|||
minor | ||||
minor | ||||
minor | ||||
no | ||||
no | ||||
no | ||||
no | ||||
yes | ||||
yes | ||||
yes | ||||
yes | ||||
yes | ||||
yes | ||||
yes |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
PubMed
Title | Date | PubMed |
---|---|---|
Papaverine, drug-induced stereotypy and catalepsy and biogenic amines in the brain of the rat. | 1976 Jul |
|
Effect of angiotensin on the central action of dopamine. | 1976 Nov-Dec |
|
Parkinsonism by haloperidol and piribedil. | 1978 Oct 31 |
|
Effect of drugs influencing central serotonergic mechanisms on haloperidol-induced catalepsy. | 1979 Mar 29 |
|
Behavioral changes as a result of dotarizine or flunarizine influence on dopaminergic neurotransmission in the striatum. | 1998 |
|
The anticataleptic effect of 7-OH-DPAT: are dopamine D3 receptors involved? | 1999 |
|
Locomotor activity and accumbens Fos expression driven by ventral hippocampal stimulation require D1 and D2 receptors. | 1999 |
|
L-701,324, a selective antagonist at the glycine site of the NMDA receptor, counteracts haloperidol-induced muscle rigidity in rats. | 1999 Apr |
|
Impaired extrapyramidal function caused by the targeted disruption of retinoid X receptor RXRgamma1 isoform. | 1999 Apr |
|
Sexual disturbances during clozapine and haloperidol treatment for schizophrenia. | 1999 Apr |
|
Neuroleptic malignant syndrome induced by haloperidol following traumatic brain injury. | 1999 Dec |
|
Evidence of sex related differences in the effects of calcium channel blockers on neuroleptic-induced catalepsy in mice. | 1999 Feb |
|
Atrophic and static (neurodevelopmental) schizophrenic psychoses: premorbid functioning, symptoms and neuroleptic response. | 1999 Jul |
|
Clozapine pretreatment modifies haloperidol-elicited forebrain Fos induction: a regionally-specific double dissociation. | 1999 Jun |
|
Interaction between olanzapine and haloperidol. | 1999 Jun |
|
The effects of dopamine D2 and D3 antagonists on spontaneous motor activity and morphine-induced hyperactivity in male mice. | 1999 Mar |
|
Methamphetamine-associated obsessional symptoms and effective risperidone treatment: a case report. | 1999 May |
|
Quinpirole, 8-OH-DPAT and ketanserin modulate catalepsy induced by high doses of atypical antipsychotics. | 1999 Nov |
|
The effects of benzamide analogues on cocaine self-administration in rhesus monkeys. | 1999 Nov |
|
Actions of adenosine A2A receptor antagonist KW-6002 on drug-induced catalepsy and hypokinesia caused by reserpine or MPTP. | 1999 Nov |
|
Efficacy of pramipexole, a new dopamine receptor agonist, to relieve the parkinsonian-like muscle rigidity in rats. | 1999 Nov 26 |
|
Inhibition of haloperidol-induced catalepsy in rats by root extracts from Piper methysticum F. | 1999 Oct |
|
Haloperidol-induced torsade de pointes. | 1999 Oct |
|
Enhanced striatal dopamine D(2) receptor-induced [35S]GTPgammaS binding after haloperidol treatment. | 1999 Oct 8 |
|
Two additional uses for sildenafil in psychiatric patients. | 1999 Oct-Dec |
|
A case of leukocytoclastic vasculitis associated with haloperidol. | 1999 Sep |
|
Effects of SCH 23390, raclopride, and haloperidol on morphine withdrawal-induced aggression in male mice. | 1999 Sep |
|
Risperidone in treatment-refractory schizophrenia. | 1999 Sep |
|
The role of metabotropic glutamate receptor (mGluR) ligands in parkinsonian muscle rigidity. | 2000 |
|
Effect of muscarinic receptor agonists on animal models of psychosis. | 2000 Apr |
|
Inhibition by various antipsychotic drugs of the G-protein-activated inwardly rectifying K(+) (GIRK) channels expressed in xenopus oocytes. | 2000 Apr |
|
Prolonged upper airway instability in the parenteral use of benzodiazepine with levomepromazine. | 2000 Feb |
|
Sub-chronic inhibition of nitric-oxide synthesis modifies haloperidol-induced catalepsy and the number of NADPH-diaphorase neurons in mice. | 2000 Jan |
|
Reduced number of striatal neurons expressing preprosomatostatin mRNA in rats with oral dyskinesias after long-term haloperidol administration. | 2000 Jan 21 |
|
Prolactin regulation of tuberoinfundibular dopaminergic neurons: immunoneutralization studies. | 2000 Jan 3 |
|
The antidepressive-like effect of oxcarbazepine: possible role of dopaminergic neurotransmission. | 2000 Jul |
|
Further evidence that behavioral tests and neuropeptide mRNA and tissue level alterations can differentiate between typical and atypical antipsychotic drugs. | 2000 Jul |
|
Effect of magnesium sulfate on the haloperidol-induced QT prolongation assessed in the canine in vivo model under the monitoring of monophasic action potential. | 2000 Jun |
|
Double blind study of tiapride versus haloperidol and placebo in agitation and aggressiveness in elderly patients with cognitive impairment. | 2000 Mar |
|
Effect of dopamine agonists and antagonists on the lorazepam withdrawal syndrome in rats. | 2000 Mar |
|
Torsades de pointes secondary to intravenous haloperidol after coronary bypass grafting surgery. | 2000 Mar |
|
Effects of atypical neuroleptics on sustained attention deficits in schizophrenia: a trial of risperidone versus haloperidol. | 2000 Mar |
|
No changes in dopamine D(1) receptor mRNA expressing neurons in the dorsal striatum of rats with oral movements induced by long-term haloperidol administration. | 2000 Mar 24 |
|
Propiverine-induced Parkinsonism: a case report and a pharmacokinetic/pharmacodynamic study in mice. | 2000 May |
|
Doses of olanzapine, risperidone, and haloperidol used in clinical practice: results of a prospective pharmacoepidemiologic study. EFESO Study Group. Estudio Farmacoepidemiologico en la Esquizofrenia con Olanzapina. | 2000 May |
|
The safety of olanzapine compared with other antipsychotic drugs: results of an observational prospective study in patients with schizophrenia (EFESO Study). Pharmacoepidemiologic Study of Olanzapine in Schizophrenia. | 2000 May |
|
Haloperidol-induced catalepsy is influenced by calcium channel antagonists. | 2000 May-Jun |
|
Enhancement of haloperidol-induced catalepsy by nicotine: an investigation of possible mechanisms. | 2000 Nov |
|
Role of prolactin in chloro-S-triazine rat mammary tumorigenesis. | 2000 Nov |
|
Contrasting patterns and cellular specificity of transcriptional regulation of the nuclear receptor nerve growth factor-inducible B by haloperidol and clozapine in the rat forebrain. | 2000 Oct |
Sample Use Guides
In Vivo Use Guide
Curator's Comment: can also be taken orally https://www.drugs.com/ppa/haloperidol.html
Parenteral medication, administered intramuscularly in doses of 2 to 5 mg, is utilized for prompt control of the acutely agitated schizophrenic patient with moderately severe to very severe symptoms. Depending on the response of the patient, subsequent doses may be given, administered as often as every hour, although 4 to 8 hour intervals may be satisfactory.
Route of Administration:
Intramuscular
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/25572138
10 uM Haloperidol induced a 54% decrease in the mRNA expression of ABCA1 in murineperitoneal macrophages.
Substance Class |
Chemical
Created
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admin
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Edited
Mon Mar 31 18:25:58 GMT 2025
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Record UNII |
6387S86PK3
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Record Status |
Validated (UNII)
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Record Version |
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NCI_THESAURUS |
C66883
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217483
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100000086697
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Related Record | Type | Details | ||
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IMPURITY -> PARENT |
HALOPERIDOL LACTATE FROM TABLETS
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Related Record | Type | Details | ||
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ACTIVE MOIETY |