Details
Stereochemistry | ACHIRAL |
Molecular Formula | C21H23ClFNO2 |
Molecular Weight | 375.864 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
OC1(CCN(CCCC(=O)C2=CC=C(F)C=C2)CC1)C3=CC=C(Cl)C=C3
InChI
InChIKey=LNEPOXFFQSENCJ-UHFFFAOYSA-N
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
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 |
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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 |
Doses
Dose | Population | Adverse events |
---|---|---|
0.9 mg single, oral Overdose |
unknown, 11 years n = 1 Health Status: unknown Age Group: 11 years Sex: M Population Size: 1 Sources: |
Other AEs: Drowsiness... |
2 mg 4 times / day multiple, intramuscular Recommended Dose: 2 mg, 4 times / day Route: intramuscular Route: multiple Dose: 2 mg, 4 times / day Sources: |
unhealthy, adult Health Status: unhealthy Condition: dementia-related psychosis Age Group: adult Sources: |
|
5 mg 3 times / day multiple, oral Recommended Dose: 5 mg, 3 times / day Route: oral Route: multiple Dose: 5 mg, 3 times / day Sources: |
unhealthy, adult Health Status: unhealthy Condition: dementia-related psychosis Age Group: adult Sources: |
|
10 mg 2 times / day steady, intravenous Dose: 10 mg, 2 times / day Route: intravenous Route: steady Dose: 10 mg, 2 times / day Sources: |
unhealthy n = 192 Health Status: unhealthy Condition: Delirium Population Size: 192 Sources: |
Other AEs: Torsades de pointes, Electrocardiogram QTc interval prolonged... Other AEs: Torsades de pointes (serious, 2 patients) Sources: Electrocardiogram QTc interval prolonged (below serious, 13 patients) |
10 mg 2 times / day steady, oral Dose: 10 mg, 2 times / day Route: oral Route: steady Dose: 10 mg, 2 times / day Sources: |
unhealthy n = 20 Health Status: unhealthy Condition: Bipolar I Disorder Population Size: 20 Sources: |
Other AEs: Cheilitis, Constipation... Other AEs: Cheilitis (below serious, 1 patient) Sources: Constipation (below serious, 2 patients) Salivary hypersecretion (below serious, 1 patient) Vomiting (below serious, 1 patient) Malaise (below serious, 2 patients) Thirst (below serious, 1 patient) Fall (below serious, 1 patient) Blood pressure decreased (below serious, 1 patient) Weight increased (below serious, 1 patient) Increased appetite (below serious, 1 patient) Arthralgia (below serious, 1 patient) Osteoarthritis (below serious, 1 patient) Akathisia (below serious, 3 patients) Dystonia (below serious, 3 patients) Headache (below serious, 1 patient) Sedation (below serious, 1 patient) Tremor (below serious, 2 patients) Depressive symptom (below serious, 1 patient) Insomnia (below serious, 1 patient) Mania (below serious, 1 patient) Pruritus (below serious, 1 patient) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Drowsiness | 1 patient | 0.9 mg single, oral Overdose |
unknown, 11 years n = 1 Health Status: unknown Age Group: 11 years Sex: M Population Size: 1 Sources: |
Electrocardiogram QTc interval prolonged | below serious, 13 patients | 10 mg 2 times / day steady, intravenous Dose: 10 mg, 2 times / day Route: intravenous Route: steady Dose: 10 mg, 2 times / day Sources: |
unhealthy n = 192 Health Status: unhealthy Condition: Delirium Population Size: 192 Sources: |
Torsades de pointes | serious, 2 patients | 10 mg 2 times / day steady, intravenous Dose: 10 mg, 2 times / day Route: intravenous Route: steady Dose: 10 mg, 2 times / day Sources: |
unhealthy n = 192 Health Status: unhealthy Condition: Delirium Population Size: 192 Sources: |
Arthralgia | below serious, 1 patient | 10 mg 2 times / day steady, oral Dose: 10 mg, 2 times / day Route: oral Route: steady Dose: 10 mg, 2 times / day Sources: |
unhealthy n = 20 Health Status: unhealthy Condition: Bipolar I Disorder Population Size: 20 Sources: |
Blood pressure decreased | below serious, 1 patient | 10 mg 2 times / day steady, oral Dose: 10 mg, 2 times / day Route: oral Route: steady Dose: 10 mg, 2 times / day Sources: |
unhealthy n = 20 Health Status: unhealthy Condition: Bipolar I Disorder Population Size: 20 Sources: |
Cheilitis | below serious, 1 patient | 10 mg 2 times / day steady, oral Dose: 10 mg, 2 times / day Route: oral Route: steady Dose: 10 mg, 2 times / day Sources: |
unhealthy n = 20 Health Status: unhealthy Condition: Bipolar I Disorder Population Size: 20 Sources: |
Depressive symptom | below serious, 1 patient | 10 mg 2 times / day steady, oral Dose: 10 mg, 2 times / day Route: oral Route: steady Dose: 10 mg, 2 times / day Sources: |
unhealthy n = 20 Health Status: unhealthy Condition: Bipolar I Disorder Population Size: 20 Sources: |
Fall | below serious, 1 patient | 10 mg 2 times / day steady, oral Dose: 10 mg, 2 times / day Route: oral Route: steady Dose: 10 mg, 2 times / day Sources: |
unhealthy n = 20 Health Status: unhealthy Condition: Bipolar I Disorder Population Size: 20 Sources: |
Headache | below serious, 1 patient | 10 mg 2 times / day steady, oral Dose: 10 mg, 2 times / day Route: oral Route: steady Dose: 10 mg, 2 times / day Sources: |
unhealthy n = 20 Health Status: unhealthy Condition: Bipolar I Disorder Population Size: 20 Sources: |
Increased appetite | below serious, 1 patient | 10 mg 2 times / day steady, oral Dose: 10 mg, 2 times / day Route: oral Route: steady Dose: 10 mg, 2 times / day Sources: |
unhealthy n = 20 Health Status: unhealthy Condition: Bipolar I Disorder Population Size: 20 Sources: |
Insomnia | below serious, 1 patient | 10 mg 2 times / day steady, oral Dose: 10 mg, 2 times / day Route: oral Route: steady Dose: 10 mg, 2 times / day Sources: |
unhealthy n = 20 Health Status: unhealthy Condition: Bipolar I Disorder Population Size: 20 Sources: |
Mania | below serious, 1 patient | 10 mg 2 times / day steady, oral Dose: 10 mg, 2 times / day Route: oral Route: steady Dose: 10 mg, 2 times / day Sources: |
unhealthy n = 20 Health Status: unhealthy Condition: Bipolar I Disorder Population Size: 20 Sources: |
Osteoarthritis | below serious, 1 patient | 10 mg 2 times / day steady, oral Dose: 10 mg, 2 times / day Route: oral Route: steady Dose: 10 mg, 2 times / day Sources: |
unhealthy n = 20 Health Status: unhealthy Condition: Bipolar I Disorder Population Size: 20 Sources: |
Pruritus | below serious, 1 patient | 10 mg 2 times / day steady, oral Dose: 10 mg, 2 times / day Route: oral Route: steady Dose: 10 mg, 2 times / day Sources: |
unhealthy n = 20 Health Status: unhealthy Condition: Bipolar I Disorder Population Size: 20 Sources: |
Salivary hypersecretion | below serious, 1 patient | 10 mg 2 times / day steady, oral Dose: 10 mg, 2 times / day Route: oral Route: steady Dose: 10 mg, 2 times / day Sources: |
unhealthy n = 20 Health Status: unhealthy Condition: Bipolar I Disorder Population Size: 20 Sources: |
Sedation | below serious, 1 patient | 10 mg 2 times / day steady, oral Dose: 10 mg, 2 times / day Route: oral Route: steady Dose: 10 mg, 2 times / day Sources: |
unhealthy n = 20 Health Status: unhealthy Condition: Bipolar I Disorder Population Size: 20 Sources: |
Thirst | below serious, 1 patient | 10 mg 2 times / day steady, oral Dose: 10 mg, 2 times / day Route: oral Route: steady Dose: 10 mg, 2 times / day Sources: |
unhealthy n = 20 Health Status: unhealthy Condition: Bipolar I Disorder Population Size: 20 Sources: |
Vomiting | below serious, 1 patient | 10 mg 2 times / day steady, oral Dose: 10 mg, 2 times / day Route: oral Route: steady Dose: 10 mg, 2 times / day Sources: |
unhealthy n = 20 Health Status: unhealthy Condition: Bipolar I Disorder Population Size: 20 Sources: |
Weight increased | below serious, 1 patient | 10 mg 2 times / day steady, oral Dose: 10 mg, 2 times / day Route: oral Route: steady Dose: 10 mg, 2 times / day Sources: |
unhealthy n = 20 Health Status: unhealthy Condition: Bipolar I Disorder Population Size: 20 Sources: |
Constipation | below serious, 2 patients | 10 mg 2 times / day steady, oral Dose: 10 mg, 2 times / day Route: oral Route: steady Dose: 10 mg, 2 times / day Sources: |
unhealthy n = 20 Health Status: unhealthy Condition: Bipolar I Disorder Population Size: 20 Sources: |
Malaise | below serious, 2 patients | 10 mg 2 times / day steady, oral Dose: 10 mg, 2 times / day Route: oral Route: steady Dose: 10 mg, 2 times / day Sources: |
unhealthy n = 20 Health Status: unhealthy Condition: Bipolar I Disorder Population Size: 20 Sources: |
Tremor | below serious, 2 patients | 10 mg 2 times / day steady, oral Dose: 10 mg, 2 times / day Route: oral Route: steady Dose: 10 mg, 2 times / day Sources: |
unhealthy n = 20 Health Status: unhealthy Condition: Bipolar I Disorder Population Size: 20 Sources: |
Akathisia | below serious, 3 patients | 10 mg 2 times / day steady, oral Dose: 10 mg, 2 times / day Route: oral Route: steady Dose: 10 mg, 2 times / day Sources: |
unhealthy n = 20 Health Status: unhealthy Condition: Bipolar I Disorder Population Size: 20 Sources: |
Dystonia | below serious, 3 patients | 10 mg 2 times / day steady, oral Dose: 10 mg, 2 times / day Route: oral Route: steady Dose: 10 mg, 2 times / day Sources: |
unhealthy n = 20 Health Status: unhealthy Condition: Bipolar I Disorder Population Size: 20 Sources: |
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 |
---|---|---|
Extrapyramidal reactions and amine metabolites in cerebrospinal fluid during haloperidol and clozapine treatment of schizophrenic patients. | 1975 |
|
A comparative study of haloperidol and chlorpromazine in terms of clinical effects and therapeutic reversal with benztropine in schizophrenia. Theoretical implications for potency differences among neuroleptics. | 1975 Aug 21 |
|
Atypical tardive dyskinesia. | 1975 May |
|
Parkinsonism by haloperidol and piribedil. | 1978 Oct 31 |
|
Modulatory effects of PLG and its peptidomimetics on haloperidol-induced catalepsy in rats. | 1999 |
|
Synthesis and preliminary pharmacological investigations of 1-(1,2-dihydro-2-acenaphthylenyl)piperazine derivatives as potential atypical antipsychotic agents in mice. | 1999 Aug 30 |
|
Reduced haloperidol does not interfere with the antipsychotic activity of haloperidol in the treatment of acute schizophrenia. | 1999 Jul |
|
Tardive dystonia induced by risperidone. | 1999 Jun |
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Interaction between olanzapine and haloperidol. | 1999 Jun |
|
Quinpirole, 8-OH-DPAT and ketanserin modulate catalepsy induced by high doses of atypical antipsychotics. | 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 |
|
Identification of quantitative trait loci for haloperidol-induced catalepsy on mouse chromosome 14. | 1999 Sep |
|
Inhibition by various antipsychotic drugs of the G-protein-activated inwardly rectifying K(+) (GIRK) channels expressed in xenopus oocytes. | 2000 Apr |
|
Sildenafil and erectile dysfunction. | 2000 Dec |
|
Risperidone versus haloperidol in psychotic patients with disturbing neuroleptic-induced extrapyramidal symptoms: a double-blind, multi-center trial. | 2000 Dec 15 |
|
Sub-chronic inhibition of nitric-oxide synthesis modifies haloperidol-induced catalepsy and the number of NADPH-diaphorase neurons in mice. | 2000 Jan |
|
Manic episode in an ifosfamide-treated patient. | 2000 Jan-Feb |
|
Repeated treatment with 8-OH-DPAT induces tolerance to its ability to produce the 5-HT1A behavioural syndrome, but not to its ability to attenuate haloperidol-induced catalepsy. | 2000 Jun |
|
Effect of dopamine agonists and antagonists on the lorazepam withdrawal syndrome in rats. | 2000 Mar |
|
Role of prolactin in chloro-S-triazine rat mammary tumorigenesis. | 2000 Nov |
|
Neurotensin gene expression and behavioral responses following administration of psychostimulants and antipsychotic drugs in dopamine D(3) receptor deficient mice. | 2001 Feb |
|
Double activity imaging reveals distinct cellular targets of haloperidol, clozapine and dopamine D(3) receptor selective RGH-1756. | 2001 Mar |
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.
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Classification Tree | Code System | Code | ||
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LIVERTOX |
NBK548393
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NDF-RT |
N0000180182
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WHO-ATC |
N05AD01
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WHO-ESSENTIAL MEDICINES LIST |
24.1
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WHO-VATC |
QN05AD01
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NCI_THESAURUS |
C323
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NCI_THESAURUS |
C66883
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Code System | Code | Type | Description | ||
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HALOPERIDOL
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PRIMARY | Description: A white to faintly yellowish, amorphous or microcrystalline powder; odourless. Solubility: Practically insoluble in water; soluble in 50 parts of ethanol (~750 g/l) TS and in 200 parts of ether R. Category: Neuroleptic. Storage: Haloperidol should be kept in a well-closed container, protected from light. Definition: Haloperidol contains not less than 98.0% and not more than 101.0% of C21H23ClFNO2, calculated with reference to the dried substance. | ||
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86
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1303002
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5613
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DB00502
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J6292F8L3D
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3093
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Haloperidol
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HALOPERIDOL
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J6292F8L3D
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5093
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52-86-8
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3559
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CHEMBL54
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D006220
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200-155-6
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m5904
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615296
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C537
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DTXSID4034150
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100000092645
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SUB08005MIG
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918
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170973
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1353
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ACTIVE MOIETY
METABOLITE (PARENT)
METABOLITE (PARENT)
METABOLITE (PARENT)
METABOLITE INACTIVE (PARENT)
METABOLITE TOXIC (PARENT)
PARENT (METABOLITE)
PRODRUG (METABOLITE ACTIVE)
SALT/SOLVATE (PARENT)