ContaminantDB: Haloperidol

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Targets (30)XML

Record Information

Version

1.0

Creation Date

2009-07-05 03:35:09 UTC

Update Date

2026-05-14 16:40:38 UTC

Accession Number

CHEM002100

Identification

Common Name

Haloperidol

Class

Small Molecule

Description

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)

Contaminant Sources

HMDB Contaminants - Urine
STOFF IDENT Compounds
T3DB toxins
ToxCast & Tox21 Chemicals

Contaminant Type

Amine
Antidyskinetic
Antiemetic
Antipsychotic Agent
Butyrophenone
Dopamine Antagonist
Drug
Ester
Human Neurotoxin
Metabolite
Organic Compound
Organochloride
Organofluoride
Synthetic Compound

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Value	Source
1-(3-p-Fluorobenzoylpropyl)-4-p-chlorophenyl-4-hydroxypiperidine	ChEBI
4'-Fluoro-4-(4-(p-chlorophenyl)-4-hydroxypiperidinyl)butyrophenone	ChEBI
4'-Fluoro-4-(4-hydroxy-4-(4'-chlorophenyl)piperidino)butyrophenone	ChEBI
4-(4-(Para-chlorophenyl)-4-hydroxypiperidino)-4'-fluorobutyrophenone	ChEBI
4-[4-(4-Chlorophenyl)-4-hydroxy-1-piperidyl]-1-(4-fluorophenyl)-butan-1-one	ChEBI
gamma-(4-(p-Chlorophenyl)-4-hydroxpiperidino)-p-fluorbutyrophenone	ChEBI
Haldol	ChEBI
Haloperidolum	ChEBI
g-(4-(p-Chlorophenyl)-4-hydroxpiperidino)-p-fluorbutyrophenone	Generator
Γ-(4-(p-chlorophenyl)-4-hydroxpiperidino)-p-fluorbutyrophenone	Generator

Chemical Formula

C₂₁H₂₃ClFNO₂

Average Molecular Mass

375.864 g/mol

Monoisotopic Mass

375.140 g/mol

CAS Registry Number

52-86-8

IUPAC Name

4-[4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl]-1-(4-fluorophenyl)butan-1-one

Traditional Name

haloperidol

SMILES

OC1(CCN(CCCC(=O)C2=CC=C(F)C=C2)CC1)C1=CC=C(Cl)C=C1

InChI Identifier

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

InChI Key

LNEPOXFFQSENCJ-UHFFFAOYSA-N

Chemical Taxonomy

Description

belongs to the class of organic compounds known as alkyl-phenylketones. These are aromatic compounds containing a ketone substituted by one alkyl group, and a phenyl group.

Kingdom

Organic compounds

Super Class

Organic oxygen compounds

Class

Organooxygen compounds

Sub Class

Carbonyl compounds

Direct Parent

Alkyl-phenylketones

Alternative Parents

Substituents

Alkyl-phenylketone
Phenylpiperidine
Butyrophenone
Phenylbutylamine
Benzoyl
Aryl alkyl ketone
Aralkylamine
Chlorobenzene
Fluorobenzene
Halobenzene
Aryl chloride
Aryl fluoride
Aryl halide
Monocyclic benzene moiety
Gamma-aminoketone
Benzenoid
Piperidine
Tertiary alcohol
Tertiary amine
Tertiary aliphatic amine
Azacycle
Organoheterocyclic compound
Organofluoride
Organochloride
Organohalogen compound
Amine
Organic nitrogen compound
Alcohol
Organonitrogen compound
Organopnictogen compound
Organic oxide
Hydrocarbon derivative
Aromatic heteromonocyclic compound

Molecular Framework

Aromatic heteromonocyclic compounds

External Descriptors

organofluorine compound (CHEBI:5613 )
tertiary alcohol (CHEBI:5613 )
monochlorobenzenes (CHEBI:5613 )
aromatic ketone (CHEBI:5613 )
hydroxypiperidine (CHEBI:5613 )

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

Cellular Locations

Cytoplasm
Membrane

Biofluid Locations

Not Available

Tissue Locations

Not Available

Pathways

Not Available

Applications

Biological Roles

Chemical Roles

Not Available

Physical Properties

State

Solid

Appearance

White to faintly yellowish, amorphous or micro-crystalline powder (4).

Experimental Properties

Property	Value
Melting Point	151.5°C
Boiling Point	Not Available
Solubility	14 mg/L (at 25°C)

Predicted Properties

Property	Value	Source
Water Solubility	0.0045 g/L	ALOGPS
logP	3.7	ALOGPS
logP	3.66	ChemAxon
logS	-4.9	ALOGPS
pKa (Strongest Acidic)	13.96	ChemAxon
pKa (Strongest Basic)	8.05	ChemAxon
Physiological Charge	1	ChemAxon
Hydrogen Acceptor Count	3	ChemAxon
Hydrogen Donor Count	1	ChemAxon
Polar Surface Area	40.54 Å²	ChemAxon
Rotatable Bond Count	6	ChemAxon
Refractivity	102.59 m³·mol⁻¹	ChemAxon
Polarizability	39.15 Å³	ChemAxon
Number of Rings	3	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	View
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-00di-3941000000-d115a40817bca84c859a	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positive	splash10-00di-5941100000-c3840be760880e2d998a	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF , positive	splash10-004i-0009000000-cdfdd91dd85d2c1cbd3d	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF , positive	splash10-00or-0409000000-d542c35143556b83b87a	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF , positive	splash10-014i-0900000000-3985dded029c89448ebe	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF , positive	splash10-01b9-0900000000-720c0a4f1130b4237f32	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF , positive	splash10-00di-0900000000-772a799ebb3b949cef0c	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , positive	splash10-004i-0009000000-21c8918254235e561129	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , positive	splash10-014i-0904000000-8c97cb39f9680dd91378	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , positive	splash10-01b9-0900000000-571a03ebb5faa3e5cd63	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , positive	splash10-00di-0900000000-62e233fd691121c78e96	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , positive	splash10-00di-0900000000-91bf80d34ef94ed709f0	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , positive	splash10-00di-0900000000-46ef29917220709863a4	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , positive	splash10-00di-3900000000-26f391756d439f7dbfc8	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , positive	splash10-00b9-9600000000-404fc399b40cfb560a99	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , positive	splash10-00b9-9100000000-8779758823471091566a	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - , positive	splash10-004i-1619000000-27aa28ad7f91429f5ae7	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - , positive	splash10-004i-0609000000-f7c623630d33dbd89e2b	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - , positive	splash10-01b9-3911000000-78d5b34044714e81aec3	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 30V, Positive	splash10-014i-0904000000-de8db1cf24411de5c68b	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 20V, Positive	splash10-00or-0409000000-36213f9899b1353ed71a	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-0a6r-0009000000-abe4b4cad1298a753614	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-0a6r-0679000000-5910dd3a7977bc423000	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-00l6-4961000000-075c4f60c9298ff5cd1e	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-00di-0009000000-c5a2526394d0eaf36160	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-00di-1329000000-8e1f1a55517bf6e11ca4	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-03dj-3920000000-2f2c54905c928d8238fb	Spectrum
MS	Mass Spectrum (Electron Ionization)	splash10-0079-3290000000-cc6a990404ba7b9452a8	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum

Toxicity Profile

Route of Exposure

Inhalation, Oral (60%)

Mechanism of Toxicity

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.

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 (3, 2, 3). Half Life: 3 weeks

Toxicity Values

LD50: 128 mg/kg (Oral, Rat) LD50: 71 mg/kg (Oral, Mouse) LD50: 90 mg/kg (Oral, Dog) LD50: 165 mg/kg (Oral, Rat)

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

No indication of carcinogenicity to humans (not listed by IARC).

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.

Minimum Risk Level

Not Available

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. (7)

Concentrations

Not Available

External Links

DrugBank ID

DB00502

HMDB ID

HMDB0014645

FooDB ID

FDB009770

Phenol Explorer ID

Not Available

KNApSAcK ID