Identification

Name
Haloperidol
Accession Number
DB00502  (APRD00538)
Type
Small Molecule
Groups
Approved
Description

A phenyl-piperidinyl-butyrophenone, traditional antipsychotic drug that is used primarily to treat schizophrenia and other psychoses. It is also used for the management of schizoaffective disorder, delusional disorders, ballism, and Tourette syndrome (a drug of choice) and occasionally as adjunctive therapy in mental retardation and the chorea associated with Huntington's disease. It is a potent antiemetic and is used in the treatment of intractable hiccups [5], [7].

The efficacy of haloperidol was first established in controlled trials in the 1960s [9].

Interestingly, in vivo pharmacogenetic studies have demonstrated that the metabolism of haloperidol may be modulated by genetically determined polymorphic CYP2D6 activity. However, these findings contradict the findings from studies in vitro with human liver microsomes and from drug interaction studies in vivo. Inter-ethnic and pharmacogenetic differences in haloperidol metabolism may possibly explain these observations [3].

Structure
Thumb
Synonyms
  • 1-(3-p-fluorobenzoylpropyl)-4-p-chlorophenyl-4-hydroxypiperidine
  • 4-(4-(para-chlorophenyl)-4-hydroxypiperidino)-4'-fluorobutyrophenone
  • 4-[4-(4-chlorophenyl)-4-hydroxy-1-piperidyl]-1-(4-fluorophenyl)-butan-1-one
  • 4'-fluoro-4-(4-(p-chlorophenyl)-4-hydroxypiperidinyl)butyrophenone
  • 4'-fluoro-4-(4-hydroxy-4-(4'-chlorophenyl)piperidino)butyrophenone
  • Haloperidolum
  • γ-(4-(p-chlorophenyl)-4-hydroxpiperidino)-p-fluorbutyrophenone
External IDs
MCN-JR-1625 / NSC-170973 / NSC-615296 / R-1625
Product Ingredients
IngredientUNIICASInChI Key
Haloperidol decanoateAC20PJ410174050-97-8GUTXTARXLVFHDK-UHFFFAOYSA-N
Haloperidol lactate6387S86PK353515-91-6BVUSNQJCSYDJJG-UHFFFAOYSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo Haloperidol Liq 2mg/mlSolution2 mgOralApotex Corporation1983-12-31Not applicableCanada
Apo Haloperidol Tab 0.5mgTablet.5 mgOralApotex Corporation1980-12-31Not applicableCanada
Apo Haloperidol Tab 1mgTablet1 mgOralApotex Corporation1980-12-31Not applicableCanada
HaldolInjection, solution5 mg/1mLIntramuscularMcNeil Pharmaceuticals1971-05-182011-07-31Us
HaldolInjection5 mg/1mLIntramuscularJanssen Pharmaceuticals1971-05-18Not applicableUs
Haldol DecanoateInjection50 mg/1mLIntramuscularPhysicians Total Care, Inc.1986-01-142012-06-30Us
Haldol DecanoateInjection50 mg/1mLIntramuscularMcNeil Pharmaceuticals1986-01-142011-05-31Us
Haldol DecanoateInjection50 mg/1mLIntramuscularJanssen Pharmaceuticals, Inc.1986-01-14Not applicableUs
Haldol DecanoateInjection100 mg/1mLIntramuscularMcNeil Pharmaceuticals1986-01-142011-05-31Us
Haldol DecanoateInjection100 mg/1mLIntramuscularJanssen Pharmaceuticals, Inc.1986-01-14Not applicableUs
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-haloperidol LA InjectableLiquid100 mgIntramuscularApotex Corporation2000-06-302013-08-02Canada
Apo-haloperidol LA InjectableLiquid50 mgIntramuscularApotex Corporation2000-06-302013-08-02Canada
Apo-haloperidol Tab 10mgTablet10 mgOralApotex Corporation1987-12-31Not applicableCanada
Apo-haloperidol Tab 2mgTablet2 mgOralApotex Corporation1987-12-31Not applicableCanada
Apo-haloperidol Tab 5mgTablet5 mgOralApotex Corporation1987-12-31Not applicableCanada
HaloperidolTablet1 mg/1OralRemedy Repack2007-05-142017-02-28Us
HaloperidolTablet1 mg/1OralCardinal Health1986-11-17Not applicableUs00781 1392 01 nlmimage10 613db08d
HaloperidolTablet0.5 mg/1OralPhysicians Total Care, Inc.1999-04-29Not applicableUs54868 257020180907 15195 seh4cb
HaloperidolTablet5 mg/1OralProficient Rx LP1986-11-17Not applicableUs
HaloperidolTablet0.5 mg/1OralMylan Institutional2004-02-01Not applicableUs
International/Other Brands
Aloperidin (Janssen-Cilag) / Bioperidolo (Firma) / Brotopon (Pfizer) / Dozic (Rosemont) / Duraperidol / Einalon S / Eukystol (Merckle) / Halosten (Shionogi Seiyaku) / Keselan (Sumitomo) / Linton (Tanabe Mitsubishi Pharma) / Peluces (lsei) / Serenace (Pfizer) / Sigaperidol (Siegfried)
Categories
UNII
J6292F8L3D
CAS number
52-86-8
Weight
Average: 375.864
Monoisotopic: 375.140134897
Chemical Formula
C21H23ClFNO2
InChI Key
LNEPOXFFQSENCJ-UHFFFAOYSA-N
InChI
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
IUPAC Name
4-[4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl]-1-(4-fluorophenyl)butan-1-one
SMILES
OC1(CCN(CCCC(=O)C2=CC=C(F)C=C2)CC1)C1=CC=C(Cl)C=C1

Pharmacology

Indication

For the treatment of schizophrenia [10]

For the treatment of acute psychosis in acutely agitated schizophrenic patients with moderately severe to very severe symptoms [10]

For the treatment of severe behavioral or psychological symptoms of dementia [10]

For the treatment of delirium in the pediatric intensive care unit [10]

For the treatment of agitation or delirium [10]

For agitation† or delirium in adult patients with no underlying psychiatric illness [10]

For use as a second-line agent for rescue treatment of chemotherapy-induced nausea/vomiting [10]

For the treatment of irritability associated with autistic disorder [10]

For the treatment of tics and vocal utterances associated with Tourette's syndrome [10]

For the treatment of severe behavioral problems associated with oppositional defiant disorder or other disruptive behavioral disorders, or for the treatment of attention-deficit hyperactivity disorder (ADHD) in pediatric patients who show excessive motor activity with accompanying conduct disorders [10]

Associated Conditions
Pharmacodynamics

Haloperidol is a psychotropic agent. The drug has action at all levels of the central nervous system-primarily at subcortical levels-as well as on several organ systems. Haloperidol has potent neuroleptic antiadrenergic activity and weak peripheral anticholinergic activity, as well as minor ganglionic binding ability. It also possesses slight antihistaminic and anti-serotonergic activity and may also act as an anti-emetic [7].

Mechanism of action

Haloperidol inhibits the effects of dopamine and increases its turnover, however, the exact mechanism of action is not fully understood [Label]. Dopamine overactivity can be presynaptic (an excess of dopamine release from dopamine nerve terminals) or post-synaptic (an increase in the density of D2 receptors or an increase in post-receptor action) [11]. Traditional antipsychotics, such as haloperidol, bind more tightly than dopamine itself to the dopamine D2 receptor, with dissociation constants that are lower than that for dopamine [4].

It is believed that haloperidol competitively blocks post-synaptic dopamine (D2) receptors in the brain, eliminating dopamine neurotransmission and leading to the relief of delusions and hallucinations that are commonly associated with psychosis. It acts primarily on the D2-receptors and has some effect on 5-HT2 and α1-receptors, with negligible effects on dopamine D1-receptors. The drug also exerts some blockade of α-adrenergic receptors of the autonomic system [14].

Antagonistic activity regulated through dopamine D2 receptors in the chemoreceptive trigger zone (CTZ) of the brain renders its antiemetic activity [7]. Of the three D2-like receptors, only the D2 receptor is blocked by antipsychotic drugs in direct relation to their clinical antipsychotic abilities. The optimal clinical efficacy of antipsychotics is associated with the blockade of approximately 60 % - 80 % of D2 receptors in the brain [12].

Clinical brain-imaging findings show that haloperidol remains tightly bound to D2 dopamine receptors in humans undergoing 2 positron emission tomography (PET) scans with a 24h pause in between scans [4]. A common adverse effect of this drug is the development of extrapyramidal symptoms (EPS), due to the tight binding of haloperidol to the dopamine D2 receptor [Label]. Further information is found in the "Toxicity" section of this drug profile.

Due to the risk of unpleasant and sometimes lifelong extrapyramidal symptoms, newer antipsychotic medications than haloperidol have been discovered and formulated. Rapid dissociation of drugs from dopamine D2 receptors is a plausible explanation for the improved EPS profile of atypical antipsychotics such as Risperidone. This is also consistent with the theory of a lower affinity for D2 receptors for these drugs [12]. As mentioned above, haloperidol binds tightly to the dopamine receptor, potentiating the risk of extrapyramidal symptoms [4], and therefore should only been used when necessary.

TargetActionsOrganism
AD(2) dopamine receptor
antagonist
Human
UD(1A) dopamine receptor
antagonist
Human
UGlutamate receptor ionotropic, NMDA 2B
antagonist
Human
U5-hydroxytryptamine receptor 2A
other/unknown
Human
UD(3) dopamine receptor
inverse agonist
Human
UMelanin-concentrating hormone receptor 1Not AvailableHuman
USynaptic vesicular amine transporterNot AvailableHuman
Absorption

Haloperidol is well-absorbed from the gastrointestinal tract when ingested orally, however, the first-pass hepatic metabolism decreases its oral bioavailability to 40 - 75% [7].

Administration of haloperidol decanoate (the depot form of haloperidol for long-term treatment) in sesame oil results in slow release of the drug for long-term effects. The plasma concentrations of haloperidol gradually rise, reaching its peak concentration at about 6 days after the injection, with an apparent half-life of about 21 days. Steady-state plasma concentrations are achieved after the third or fourth dose [Label].

Serum concentration peaks 0.5 to 4 hours after an oral dose [7].

Volume of distribution

The apparent volume of distribution is about 20 L/kg, in concordance with the high lipophilicity of the drug [7], and largely depends on the subject [17].

Haloperidol is rapidly distributed to various tissues and organs, as indicated by the large volume of distribution (mean values 8 to 21 L/kg after intravenous dosing). Haloperidol readily crosses the blood-brain barrier. It also crosses the placenta and is excreted in breast milk [17].

Protein binding

Haloperidol circulates in the blood bound predominantly (90-94%) to plasma proteins [7].

Metabolism

Its metabolic fate has not been clearly established, it appears that haloperidol is primarily metabolized in the liver [7].

The drug is thought to be metabolized primarily 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.

Some data suggest that the reduced metabolite, hydroxyhaloperidol, has some pharmacologic activity, although its activity appears to be inferior to that of haloperidol. Urinary metabolites in rats include p-fluorophenaceturic acid, beta-p-fluorobenzoylpropionic acid, and several unidentified acids [7].

The enzymes involved in the biotransformation of haloperidol include cytochrome P450 (CYP), carbonyl reductase and uridine di-phosphoglucose glucuronosyltransferase enzymes. The greatest proportion of the intrinsic hepatic clearance of haloperidol is performed by glucuronidation and followed by the reduction of haloperidol to reduced haloperidol and by CYP-mediated oxidation.

In studies of cytochrome-mediated disposition in vitro, CYP3A4 appears to be the major isoform of the enzyme responsible for the metabolism of haloperidol in humans. The intrinsic clearance of the back-oxidation of reduced haloperidol to the parent compound, oxidative N-dealkylation and pyridinium formation are of the same order of magnitude. This suggests that the same enzyme system is responsible for the above three metabolic reactions [7].

Haloperidol is a substrate of CYP3A4 and an inhibitor, as well as a stimulator, of CYP2D6 [7].

Route of elimination

Urine 40% (1% unchanged), feces 15% [8]

Half life

For the non-decanoate formulations, the haloperidol half-life is on average 24 hours after oral administration and 21 hours after intramuscular administration [17].

Clearance

Haloperidol clearance after extravascular administration ranges from 0.9-1.5 l/h/kg, however this rate is reduced in poor metabolizers of CYP2D6 enzyme. Reduced CYP2D6 enzyme activity may result in increased concentrations of haloperidol. The inter-subject variability (coefficient of variation, %) in haloperidol clearance was estimated to be 44% in a population pharmacokinetic analysis in patients with schizophrenia [17].

Toxicity

Acute oral toxicity (LD50): 71 mg/kg in rats [MSDS].

Toxicity of haloperidol may be divided into several categories, according the FDA label:

Cardiovascular Effects

The incidence of sudden death, QT-prolongation, and Torsades de Pointes has been reported in patients treated with this drug. Higher than usual doses of any formulation and intravenous (IV) administration of haloperidol have shown to be associated with a higher risk of QT-prolongation and Torsades de Pointes [Label].

Caution is advised in treating patients with other cardiac QT-prolonging conditions (including electrolyte imbalance [particularly hypokalemia and hypomagnesemia], drugs which prolong the QT interval, underlying cardiac abnormalities, hypothyroidism, and familial long QT-syndrome). Depot haloperidol is not to be administered by the IV route [Label].

Extrapyramidal Symptoms

Extrapyramidal symptoms are comprised of a group of movement disorders which may include dystonia, akathisia, tardive dyskinesia and parkinsonism. Drug-induced extrapyramidal symptoms have been common knowledge for decades, yet the use of these drugs is still common. Despite this, these symptoms may prove to be long-lasting, and therefore, caution is warranted in the prevention of extrapyramidal symptoms [13].

Tardive Dyskinesia

This is a consisting of potentially irreversible, involuntary, dyskinetic movements may develop in patients treated with antipsychotic drugs and is known as an extrapyramidal symptom [Label]. Although the prevalence of the syndrome appears to be high among the elderly, this is a particularly common occurrence in elderly women [Label]

The risk of developing tardive dyskinesia and the risk that it may be irreversible are believed to increase as the duration of treatment and the total cumulative dose of antipsychotic drugs administered to the patient over time. However, the syndrome can develop, although much less commonly, after brief periods of treatment at lower doses [Label].

There are no known treatments for established cases of tardive dyskinesia. The syndrome may remit, partially or completely, if antipsychotic treatment is removed [Label].

Antipsychotic drugs should be prescribed in a manner that is most likely to minimize the occurrence of If signs and symptoms of tardive dyskinesia appear in a patient on antipsychotics, drug discontinuation should be considered. However, some patients may require treatment despite the presence of the syndrome [Label].

Neuroleptic Malignant Syndrome (NMS)

A potentially fatal condition, sometimes referred to as Neuroleptic Malignant Syndrome (NMS) has been demonstrated in association with antipsychotic drugs treatment. Clinical signs and symptoms of NMS are hyperpyrexia, muscle rigidity, alterations in mental status (including catatonia) and autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmias). Other signs include elevated creatine phosphokinase (CPK), myoglobinuria (rhabdomyolysis) and acute kidney failure [Label].

General

In addition to the above toxicities, number of cases of bronchopneumonia, some fatal, have followed the use of antipsychotic drugs, including haloperidol. One theory suggests that lethargy and decreased sensation of thirst due to central inhibition may lead to dehydration, hemoconcentration and reduced pulmonary ventilation. Therefore, if the above signs and symptoms appear, especially in the elderly, the physician should institute remedial therapy promptly.

Hematologic Effects

Reports have been made of the occurrence of mild, usually transient leukopenia and leukocytosis, minimal decreases in red blood cell counts, anemia, or a tendency toward monocytosis. Agranulocytosis has rarely been reported to have occurred with the use of haloperidol, and then only in association with other medication [Label].

Liver Effects

Impaired liver function and/or jaundice may occur.

Dermatologic Reactions

Maculopapular and acne-like skin reactions and isolated cases of photosensitivity and loss of hair.

Endocrine Disorders

Lactation, breast engorgement, mastalgia, menstrual irregularities, gynecomastia, impotence, increased libido, hyperglycemia, hypoglycemia and hyponatremia [Label]

Gastrointestinal Effects

Anorexia, constipation, diarrhea, hypersalivation, dyspepsia, nausea and vomiting [Label]

Autonomic Reactions

Dry mouth, blurred vision, urinary retention, diaphoresis and priapism [Label]

Respiratory Effects

Laryngospasm, bronchospasm and increased depth of respiration [Label]

Special Senses

Cataracts, retinopathy and visual disturbances [Label]

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Haloperidol.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Haloperidol.
16-BromoepiandrosteroneThe metabolism of 16-Bromoepiandrosterone can be decreased when combined with Haloperidol.
2,4-thiazolidinedioneThe therapeutic efficacy of 2,4-thiazolidinedione can be decreased when used in combination with Haloperidol.
2,5-Dimethoxy-4-ethylamphetamineHaloperidol may decrease the stimulatory activities of 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamineHaloperidol may decrease the stimulatory activities of 2,5-Dimethoxy-4-ethylthioamphetamine.
3,4-MethylenedioxyamphetamineThe risk or severity of adverse effects can be increased when 3,4-Methylenedioxyamphetamine is combined with Haloperidol.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Haloperidol.
3,5-DinitrocatecholThe therapeutic efficacy of 3,5-Dinitrocatechol can be decreased when used in combination with Haloperidol.
4-Bromo-2,5-dimethoxyamphetamineHaloperidol may decrease the stimulatory activities of 4-Bromo-2,5-dimethoxyamphetamine.
Food Interactions
  • Take with food to reduce irritation, limit caffeine intake. Avoid alcohol.

References

Synthesis Reference
US3438991
General References
  1. Niemegeers CJ, Laduron PM: Pharmacology and biochemistry of haloperidol. Proc R Soc Med. 1976;69 suppl 1:3-8. [PubMed:14331]
  2. Gelders YG: Pharmacology, pharmacokinetics and clinical development of haloperidol decanoate. Int Clin Psychopharmacol. 1986 Jul;1 Suppl 1:1-11. [PubMed:3559159]
  3. Kudo S, Ishizaki T: Pharmacokinetics of haloperidol: an update. Clin Pharmacokinet. 1999 Dec;37(6):435-56. doi: 10.2165/00003088-199937060-00001. [PubMed:10628896]
  4. Seeman P: Atypical antipsychotics: mechanism of action. Can J Psychiatry. 2002 Feb;47(1):27-38. [PubMed:11873706]
  5. Haloperidol [Link]
  6. Haloperidol PubMed Health [Link]
  7. Haloperidol PubChem [Link]
  8. Epocrates, Haloperidol [Link]
  9. Treatment mechanisms: traditional and new antipsychotic drugs [Link]
  10. Haloperidol PDR [Link]
  11. Schizophrenia: More dopamine, more D2 receptors [Link]
  12. Clinical pharmacology of atypical antipsychotics: an update [Link]
  13. Mechanism of Action of Antipsychotics, Haloperidol and Olanzapine in vitro [Link]
  14. Haloperidol Overview [Link]
  15. Haloperidol, Mental Retardation and Extrapyramidal Symptoms [Link]
  16. Haloperidol, revised [Link]
  17. Haldol Decanoate [Link]
External Links
Human Metabolome Database
HMDB0014645
KEGG Drug
D00136
KEGG Compound
C01814
PubChem Compound
3559
PubChem Substance
46508794
ChemSpider
3438
BindingDB
21398
ChEBI
5613
ChEMBL
CHEMBL54
Therapeutic Targets Database
DAP000313
PharmGKB
PA449841
IUPHAR
86
Guide to Pharmacology
GtP Drug Page
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Haloperidol
ATC Codes
N05AD01 — Haloperidol
AHFS Codes
  • 28:16.08.08 — Butyrophenones
FDA label
Download (169 KB)
MSDS
Download (73.2 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0WithdrawnTreatmentNausea / Vomiting1
1CompletedNot AvailableHealthy Volunteers1
1CompletedPreventionNicotine Dependence1
1CompletedTreatmentPsychosis1
1Unknown StatusNot AvailableHealthy Volunteers / Pharmacogenetics1
1, 2Not Yet RecruitingTreatmentAcute Polymorphic Psychotic Disorder With Symptoms of Schizophrenia / Schizophrenia and Disorders With Psychotic Features1
2Active Not RecruitingSupportive CareAdvanced Cancers1
2CompletedDiagnosticPathological Gambling1
2CompletedTreatmentAcute Agitation / Delirium / Intensive Care / Respiration, Artificial / Ventilator Weaning1
2CompletedTreatmentCognition Disorders / Delirium1
2CompletedTreatmentCritical Illness / Delirium1
2CompletedTreatmentSchizophrenic Disorders1
2RecruitingTreatmentKetamine / Violent Aggressive Behavior1
2, 3CompletedTreatmentAcute Agitation1
2, 3CompletedTreatmentAffective Disorders1
2, 3RecruitingTreatmentMalignant Neoplasms of Independent (Primary) Multiple Sites1
3Active Not RecruitingTreatmentDelirium / Impaired Cognition / Long Term Psychologic Disorders1
3Active Not RecruitingTreatmentPsychotic Disorder NOS / Schizophrenic Disorders1
3CompletedPreventionHip Fractures / Post-Operative Delirium1
3CompletedPreventionPostoperative Confusion1
3CompletedTreatmentAcute Agitation / Schizoaffective Disorders / Schizophrenic Disorders1
3CompletedTreatmentAlzheimer's Disease (AD)1
3CompletedTreatmentBipolar Disorder (BD)2
3CompletedTreatmentDelirium1
3CompletedTreatmentPsychomotor Agitation1
3CompletedTreatmentSchizophrenic Disorders4
3RecruitingTreatmentCognitive Decline / Cognitive Impairments / Critical Illness / Delirium / Intensive Care Psychosis1
3RecruitingTreatmentHypoactive Delirium1
3TerminatedTreatmentAnxiety Disorders / Dementias / Depression / Psychosomatic Disorders / Schizophrenic Disorders1
3TerminatedTreatmentConfusion and disorientation / Delirium / Postoperative / Psychomotor1
3TerminatedTreatmentDelirium3
3TerminatedTreatmentNausea / Neoplasms1
3Unknown StatusTreatmentPsychosis Nos/Other1
3WithdrawnTreatmentSchizophrenic Disorders1
4Active Not RecruitingTreatmentSchizoaffective Disorders / Schizophrenia and Disorders With Psychotic Features / Schizophrenic Disorders1
4Active Not RecruitingTreatmentSchizophrenic Disorders1
4CompletedNot AvailableSchizoaffective Disorders / Schizophrenic Disorders1
4CompletedBasic SciencePsychosis / Schizophrenic Disorders1
4CompletedPreventionCognitive Impairments / Delirium / Depression / Feeling Anxious / Post-Traumatic Stress Disorder (PTSD)1
4CompletedPreventionDelirium1
4CompletedSupportive CareDelirium / Stem Cell Transplant Complications1
4CompletedTreatmentAcute Agitation1
4CompletedTreatmentAcute Agitation / Alzheimer's Disease (AD) / Psychosis1
4CompletedTreatmentHeadaches / Migraine Disorders1
4CompletedTreatmentKetamine Induced Agitation1
4CompletedTreatmentMigrainous Headache / Nausea / Restlessness1
4CompletedTreatmentSchizoaffective Disorders / Schizophrenic Disorders3
4CompletedTreatmentSchizophrenic Disorders5
4CompletedTreatmentSubsyndromal Delirium1
4Not Yet RecruitingTreatmentAcute Agitation / Aggressive Behavior / Psychiatric Emergency1
4Not Yet RecruitingTreatmentFirst Labor Stage / Humanizing Deliver / Labor Onset / Labour Pain / Natural Childbirth / Parturition1
4RecruitingPreventionDelirium2
4RecruitingPreventionPostoperative Delirium1
4RecruitingTreatmentAcute Agitation, Behavioural Emergency1
4RecruitingTreatmentAcute Agitation / Behavioural Emergency1
4RecruitingTreatmentCannabis Use Disorders1
4RecruitingTreatmentDelirium1
4SuspendedTreatmentHyperactive Delirium / Mixed Delirium1
4SuspendedTreatmentMigrainous Headache1
4TerminatedTreatmentBipolar Disorder (BD)1
4TerminatedTreatmentGastroparesis1
4TerminatedTreatmentHaloperidol Causing Adverse Effects in Therapeutic Use / Lorazepam Causing Adverse Effects in Therapeutic Use / Loxapine Causing Adverse Effects in Therapeutic Use / Psychomotor Agitation1
4TerminatedTreatmentSchizophrenic Disorders3
4Unknown StatusTreatmentAcute Schizophrenia1
4Unknown StatusTreatmentSchizophrenia, First-Episode1
4WithdrawnTreatmentAcute Agitation1
Not AvailableActive Not RecruitingTreatmentSchizophrenia Relapse1
Not AvailableCompletedNot AvailableAcidosis, Respiratory / Movement Disorders1
Not AvailableCompletedNot AvailableBipolar Disorder (BD) / Psychotic Disorder NOS / Schizoaffective Disorders / Schizophrenic Disorders / Type 2 Diabetes Mellitus1
Not AvailableCompletedNot AvailableDyslipidemias / Insulin Resistance2
Not AvailableCompletedNot AvailableNormal Volunteers1
Not AvailableCompletedNot AvailablePsychomotor Agitation2
Not AvailableCompletedNot AvailableQT Interval Prolongation1
Not AvailableCompletedNot AvailableSchizophrenic Disorders1
Not AvailableCompletedPreventionGynecological Disease1
Not AvailableCompletedPreventionProphylaxis against postoperative nausea and vomiting1
Not AvailableCompletedScreeningBMI >30 kg/m2 / Diabetes Mellitus (DM) / Metabolic Syndromes1
Not AvailableCompletedSupportive CareFocus of Study: Absorption of the Three Components in the Topical ABH Gel in Healthy Volunteers, and Determine if There Are Any Adverse Effects / Healthy Volunteers1
Not AvailableCompletedSupportive CareNausea / Vomiting1
Not AvailableCompletedSupportive CarePatient Noncompliance1
Not AvailableCompletedTreatmentCancer, Advanced / Delirium1
Not AvailableCompletedTreatmentCognitive Impairments / Delirium1
Not AvailableCompletedTreatmentPost Streptococcal Movement Disorder / Sydenham Chorea1
Not AvailableCompletedTreatmentPsychomotor Agitation1
Not AvailableCompletedTreatmentSchizoaffective Disorders / Schizophrenic Disorders1
Not AvailableCompletedTreatmentSchizophrenic Disorders7
Not AvailableEnrolling by InvitationNot AvailableBipolar Disorder (BD)1
Not AvailableRecruitingNot AvailableAcute Bacterial Exacerbation of Chronic Bronchitis (ABECB) / Acute Bacterial Sinusitis (ABS) / Acute Decompensated Heart Failure (ADHF) / Acute Pyelonephritis / Adenovirus / Adjunct to general anesthesia therapy / Adrenal Insufficiency / Airway Swelling / Anaesthesia therapy / Anxiolysis / Arterial Hypotension / Autism, Early Infantile / Autistic Disorder / Bartonellosis / Benzodiazepine Withdrawal / Benzodiazepines / Bipolar Disorder (BD) / Bloodstream Infections / Bone and Joint Infections / Brain Swelling / Bronchospasm / Brucellosis / Cardiac Arrest / Central Nervous System Infections / Cholera / Chronic Bacterial Prostatitis / Community Acquired Pneumonia (CAP) / Complicated Urinary Tract Infections / Convulsions / Cyanide Poisoning / Cytomegalovirus Retinitis / Drug hypersensitivity reaction / Early-onset Schizophrenia Spectrum Disorders / Edema / Epilepsies / Feeling Anxious / Flu caused by Influenza / Gastroparesis / Gynaecological infection / Headaches / Herpes Simplex Virus / High Blood Cholesterol Level / High Blood Pressure (Hypertension) / Hospital-acquired bacterial pneumonia / Hyperlipidemias / Infantile Hemangiomas / Infection NOS / Inflammatory Conditions / Inflammatory Reaction / Influenza Treatment or Prophylaxis / Inhalational Anthrax (Post-Exposure) / Intra-Abdominal Infections / Life-threatening Fungal Infections / Lower Respiratory Tract Infection (LRTI) / Meningitis, Bacterial / Migraines / Muscle Spasms / Nausea / Opioid Addiction / Pain / Plague / Pneumonia / Prophylaxis / Psittacosis / Q Fever / Reflux / Relapsing Fever / Rocky Mountain Spotted Fever / Schizophrenic Disorders / Sedation therapy / Seizures / Sepsis / Skeletal Muscle Spasms / Skin and Subcutaneous Tissue Bacterial Infections / Skin Structures and Soft Tissue Infections / Stable Angina (SA) / Thromboprophylaxis / Thrombosis / Trachoma / Treatment-resistant Schizophrenia / Tularemia / Typhus Fever / Uncomplicated Skin and Skin Structure Infections / Uncomplicated Urinary Tract Infections / Urinary Tract Infections (UTIs) / Vomiting / Withdrawal1
Not AvailableRecruitingNot AvailableAdverse Drug Effect of Antipsychotics and Neuroleptics / Efficacy / Individualed Opitmal Therapy / Schizophrenic Disorders1
Not AvailableRecruitingNot AvailableSchizophrenic Disorders1
Not AvailableTerminatedTreatmentAcute Agitation / Delirium1
Not AvailableUnknown StatusTreatmentAcute Agitation1

Pharmacoeconomics

Manufacturers
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  • Marsam pharmaceuticals llc
  • Smith and nephew solopak div smith and nephew
  • Solopak medical products inc
  • Solopak laboratories inc
  • Actavis mid atlantic llc
Packagers
  • Advanced Pharmaceutical Services Inc.
  • Amerisource Health Services Corp.
  • Apotex Inc.
  • APP Pharmaceuticals
  • APPD
  • Bedford Labs
  • Ben Venue Laboratories Inc.
  • Boca Pharmacal
  • Cadila Healthcare Ltd.
  • Cardinal Health
  • Coupler Enterprises Inc.
  • Dept Health Central Pharmacy
  • Direct Dispensing Inc.
  • H.J. Harkins Co. Inc.
  • Heartland Repack Services LLC
  • Innoviant Pharmacy Inc.
  • Janssen-Ortho Inc.
  • Liberty Pharmaceuticals
  • Major Pharmaceuticals
  • Mallinckrodt Inc.
  • Mckesson Corp.
  • McNeil Laboratories
  • Medisca Inc.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Mylan
  • Neuman Distributors Inc.
  • Novex Pharma
  • Nucare Pharmaceuticals Inc.
  • OMJ Pharmaceuticals
  • Ortho Mcneil Janssen Pharmaceutical Inc.
  • Ortho-McNeil-Janssen Pharmaceuticals Inc.
  • Palmetto Pharmaceuticals Inc.
  • PCA LLC
  • PD-Rx Pharmaceuticals Inc.
  • Pharmaceutical Association
  • Pharmacia Inc.
  • Pharmacy Service Center
  • Physicians Total Care Inc.
  • Prepackage Specialists
  • Prepak Systems Inc.
  • Qualitest
  • Ranbaxy Laboratories
  • Rebel Distributors Corp.
  • Remedy Repack
  • Sandhills Packaging Inc.
  • Sandoz
  • Sicor Pharmaceuticals
  • Silarx Pharmaceuticals
  • Southwood Pharmaceuticals
  • Superior Pharmeceuticals
  • Teva Pharmaceutical Industries Ltd.
  • UDL Laboratories
  • Vangard Labs Inc.
  • Zydus Pharmaceuticals
Dosage forms
FormRouteStrength
InjectionIntramuscular100 mg/1mL
InjectionIntramuscular50 mg/1mL
InjectionIntramuscular5 mg/1
InjectionIntramuscular5 mg/1mL
Injection, solutionIntramuscular5 mg/1mL
SolutionOral2 mg/1mL
Solution, concentrateOral2 mg/1mL
TabletOral0.5 mg/1
TabletOral1 mg/1
TabletOral10 mg/1
TabletOral2 mg/1
TabletOral20 mg/1
TabletOral5 mg/1
InjectionIntramuscular141.04 mg/1mL
InjectionIntramuscular70.52 mg/1mL
Injection, solutionIntramuscular100 mg/1mL
Injection, solutionIntramuscular50 mg/1mL
Injection, solutionIntramuscular500 mg/5mL
LiquidIntramuscular50 mg
LiquidIntramuscular5 mg
SolutionIntramuscular5 mg
LiquidIntramuscular100 mg
SolutionOral2 mg
TabletOral.5 mg
TabletOral10 mg
TabletOral1 mg
TabletOral2 mg
TabletOral5 mg
SolutionIntramuscular100 mg
SolutionIntramuscular50 mg
TabletOral0.5 mg
TabletOral20 mg
Prices
Unit descriptionCostUnit
Haloperidol Decanoate 100 mg/ml Solution 5ml Vial257.14USD vial
Haldol decanoate 100 ampul107.77USD ml
Haldol decanoate 50 ampul56.53USD ml
Haloperidol dec 100 mg/ml vial29.85USD ml
Haloperidol powder21.42USD g
Haloperidol dec 50 mg/ml vial17.71USD ml
Haloperidol La 100 mg/ml15.42USD ml
Haldol 5 mg/ml ampul13.4USD ml
Haloperidol La 50 mg/ml7.71USD ml
Haloperidol 5 mg/ml4.73USD ml
Haloperidol lac 5 mg/ml vial3.54USD ml
Haloperidol 20 mg tablet2.81USD tablet
Haloperidol 10 mg tablet1.46USD tablet
Haloperidol 5 mg tablet0.8USD tablet
Novo-Peridol 20 mg Tablet0.66USD tablet
Haloperidol 2 mg tablet0.49USD tablet
Haloperidol lac 2 mg/ml conc0.45USD ml
Haloperidol 1 mg tablet0.36USD tablet
Haloperidol 0.5 mg tablet0.25USD tablet
Pernox scrub cleanser0.18USD g
Apo-Haloperidol 5 mg Tablet0.16USD tablet
Novo-Peridol 5 mg Tablet0.16USD tablet
Apo-Haloperidol 10 mg Tablet0.14USD tablet
Novo-Peridol 10 mg Tablet0.14USD tablet
Apo-Haloperidol 2 mg Tablet0.11USD tablet
Novo-Peridol 2 mg Tablet0.11USD tablet
Apo-Haloperidol 1 mg Tablet0.06USD tablet
Novo-Peridol 1 mg Tablet0.06USD tablet
Apo-Haloperidol 0.5 mg Tablet0.04USD tablet
Novo-Peridol 0.5 mg Tablet0.04USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)148MSDS
water solubility14 mg/L (at 25 °C)https://pubchem.ncbi.nlm.nih.gov/compound/haloperidol
logP4.3https://pubchem.ncbi.nlm.nih.gov/compound/haloperidol
logS-4.43https://pubchem.ncbi.nlm.nih.gov/compound/haloperidol
pKa8.66EL TAYAR,N ET AL. (1985)
Predicted Properties
PropertyValueSource
Water Solubility0.00446 mg/mLALOGPS
logP3.7ALOGPS
logP3.66ChemAxon
logS-4.9ALOGPS
pKa (Strongest Acidic)13.96ChemAxon
pKa (Strongest Basic)8.05ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area40.54 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity102.59 m3·mol-1ChemAxon
Polarizability39.15 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9465
Caco-2 permeable+0.6023
P-glycoprotein substrateSubstrate0.6673
P-glycoprotein inhibitor IInhibitor0.8563
P-glycoprotein inhibitor IIInhibitor0.8137
Renal organic cation transporterInhibitor0.6058
CYP450 2C9 substrateNon-substrate0.8355
CYP450 2D6 substrateSubstrate0.8919
CYP450 3A4 substrateSubstrate0.5796
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9207
CYP450 2D6 inhibitorInhibitor0.9197
CYP450 2C19 inhibitorNon-inhibitor0.9248
CYP450 3A4 inhibitorInhibitor0.6899
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7933
Ames testNon AMES toxic0.9133
CarcinogenicityNon-carcinogens0.8769
BiodegradationNot ready biodegradable1.0
Rat acute toxicity3.4367 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.5
hERG inhibition (predictor II)Inhibitor0.7474
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Mass Spectrum (Electron Ionization)MSsplash10-0079-3290000000-cc6a990404ba7b9452a8
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-004i-0009000000-cdfdd91dd85d2c1cbd3d
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-00or-0409000000-d542c35143556b83b87a
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-014i-0900000000-3985dded029c89448ebe
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-01b9-0900000000-720c0a4f1130b4237f32
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-00di-0900000000-772a799ebb3b949cef0c
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-004i-0009000000-21c8918254235e561129
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-014i-0904000000-8c97cb39f9680dd91378
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-01b9-0900000000-571a03ebb5faa3e5cd63
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-00di-0900000000-62e233fd691121c78e96
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-00di-0900000000-91bf80d34ef94ed709f0
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-00di-0900000000-46ef29917220709863a4
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-00di-3900000000-26f391756d439f7dbfc8
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-00b9-9600000000-404fc399b40cfb560a99
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-00b9-9100000000-8779758823471091566a
MS/MS Spectrum - , positiveLC-MS/MSsplash10-004i-1619000000-27aa28ad7f91429f5ae7
MS/MS Spectrum - , positiveLC-MS/MSsplash10-004i-0609000000-f7c623630d33dbd89e2b
MS/MS Spectrum - , positiveLC-MS/MSsplash10-01b9-3911000000-78d5b34044714e81aec3
1H NMR Spectrum1D NMRNot Applicable
13C NMR Spectrum1D NMRNot Applicable

Taxonomy

Description
This compound 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
Phenylpiperidines / Phenylbutylamines / Butyrophenones / Aryl alkyl ketones / Benzoyl derivatives / Aralkylamines / Fluorobenzenes / Chlorobenzenes / Aryl chlorides / Aryl fluorides
show 9 more
Substituents
Alkyl-phenylketone / Phenylpiperidine / Butyrophenone / Phenylbutylamine / Benzoyl / Aryl alkyl ketone / Aralkylamine / Chlorobenzene / Fluorobenzene / Halobenzene
show 23 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
organofluorine compound, tertiary alcohol, monochlorobenzenes, aromatic ketone, hydroxypiperidine (CHEBI:5613)

Targets

Details
1. D(2) dopamine receptor
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Potassium channel regulator activity
Specific Function
Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase.
Gene Name
DRD2
Uniprot ID
P14416
Uniprot Name
D(2) dopamine receptor
Molecular Weight
50618.91 Da
References
  1. Osinski MA, Uchic ME, Seifert T, Shaughnessy TK, Miller LN, Nakane M, Cox BF, Brioni JD, Moreland RB: Dopamine D2, but not D4, receptor agonists are emetogenic in ferrets. Pharmacol Biochem Behav. 2005 May;81(1):211-9. [PubMed:15894081]
  2. Bustillo J, Barrow R, Paz R, Tang J, Seraji-Bozorgzad N, Moore GJ, Bolognani F, Lauriello J, Perrone-Bizzozero N, Galloway MP: Long-term treatment of rats with haloperidol: lack of an effect on brain N-acetyl aspartate levels. Neuropsychopharmacology. 2006 Apr;31(4):751-6. [PubMed:16132064]
  3. Ishiwata K, Oda K, Sakata M, Kimura Y, Kawamura K, Oda K, Sasaki T, Naganawa M, Chihara K, Okubo Y, Ishii K: A feasibility study of [11C]SA4503-PET for evaluating sigmal receptor occupancy by neuroleptics: the binding of haloperidol to sigma1 and dopamine D2-like receptors. Ann Nucl Med. 2006 Oct;20(8):569-73. [PubMed:17134027]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  5. Naiker DV, Catts SV, Catts VS, Bedi KS, Bryan-Lluka LJ: Dose determination of haloperidol, risperidone and olanzapine using an in vivo dopamine D2-receptor occupancy method in the rat. Eur J Pharmacol. 2006 Jul 1;540(1-3):87-90. Epub 2006 May 11. [PubMed:16730699]
  6. Uchida S, Kato Y, Hirano K, Kagawa Y, Yamada S: Brain neurotransmitter receptor-binding characteristics in rats after oral administration of haloperidol, risperidone and olanzapine. Life Sci. 2007 Apr 3;80(17):1635-40. Epub 2007 Jan 27. [PubMed:17316700]
  7. Leysen JE, Janssen PM, Megens AA, Schotte A: Risperidone: a novel antipsychotic with balanced serotonin-dopamine antagonism, receptor occupancy profile, and pharmacologic activity. J Clin Psychiatry. 1994 May;55 Suppl:5-12. [PubMed:7520908]
  8. Seeman P: Dopamine D2 receptors as treatment targets in schizophrenia. Clin Schizophr Relat Psychoses. 2010 Apr;4(1):56-73. doi: 10.3371/CSRP.4.1.5. [PubMed:20643630]
Details
2. D(1A) dopamine receptor
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
G-protein coupled amine receptor activity
Specific Function
Dopamine receptor whose activity is mediated by G proteins which activate adenylyl cyclase.
Gene Name
DRD1
Uniprot ID
P21728
Uniprot Name
D(1A) dopamine receptor
Molecular Weight
49292.765 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  2. Cai G, Gurdal H, Smith C, Wang HY, Friedman E: Inverse agonist properties of dopaminergic antagonists at the D(1A) dopamine receptor: uncoupling of the D(1A) dopamine receptor from G(s) protein. Mol Pharmacol. 1999 Nov;56(5):989-96. [PubMed:10531405]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Zinc ion binding
Specific Function
NMDA receptor subtype of glutamate-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Mediated by glycine. In concert with DAPK1 at extrasynaptic site...
Gene Name
GRIN2B
Uniprot ID
Q13224
Uniprot Name
Glutamate receptor ionotropic, NMDA 2B
Molecular Weight
166365.885 Da
References
  1. Hattori K, Uchino S, Isosaka T, Maekawa M, Iyo M, Sato T, Kohsaka S, Yagi T, Yuasa S: Fyn is required for haloperidol-induced catalepsy in mice. J Biol Chem. 2006 Mar 17;281(11):7129-35. Epub 2006 Jan 10. [PubMed:16407246]
  2. Zhuravliova E, Barbakadze T, Natsvlishvili N, Mikeladze DG: Haloperidol induces neurotoxicity by the NMDA receptor downstream signaling pathway, alternative from glutamate excitotoxicity. Neurochem Int. 2007 Jun;50(7-8):976-82. Epub 2006 Nov 7. [PubMed:17092607]
  3. Gu WH, Yang S, Shi WX, Zhen XC, Jin GZ: Effects of (-)-stepholidine on NMDA receptors: comparison with haloperidol and clozapine. Acta Pharmacol Sin. 2007 Jul;28(7):953-8. [PubMed:17588330]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  5. Steinmetz RD, Fava E, Nicotera P, Steinhilber D: A simple cell line based in vitro test system for N-methyl-D-aspartate (NMDA) receptor ligands. J Neurosci Methods. 2002 Jan 15;113(1):99-110. [PubMed:11741727]
  6. Sinor JD, Du S, Venneti S, Blitzblau RC, Leszkiewicz DN, Rosenberg PA, Aizenman E: NMDA and glutamate evoke excitotoxicity at distinct cellular locations in rat cortical neurons in vitro. J Neurosci. 2000 Dec 1;20(23):8831-7. [PubMed:11102491]
  7. Gallagher MJ, Huang H, Lynch DR: Modulation of the N-methyl-D-aspartate receptor by haloperidol: NR2B-specific interactions. J Neurochem. 1998 May;70(5):2120-8. [PubMed:9572299]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Other/unknown
General Function
Virus receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including mescaline, psilocybin, 1-(2,5-dimethoxy-4-iodop...
Gene Name
HTR2A
Uniprot ID
P28223
Uniprot Name
5-hydroxytryptamine receptor 2A
Molecular Weight
52602.58 Da
References
  1. Leysen JE, Janssen PM, Megens AA, Schotte A: Risperidone: a novel antipsychotic with balanced serotonin-dopamine antagonism, receptor occupancy profile, and pharmacologic activity. J Clin Psychiatry. 1994 May;55 Suppl:5-12. [PubMed:7520908]
Details
5. D(3) dopamine receptor
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inverse agonist
General Function
G-protein coupled amine receptor activity
Specific Function
Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase. Promotes cell proliferation.
Gene Name
DRD3
Uniprot ID
P35462
Uniprot Name
D(3) dopamine receptor
Molecular Weight
44224.335 Da
References
  1. Leysen JE, Janssen PM, Megens AA, Schotte A: Risperidone: a novel antipsychotic with balanced serotonin-dopamine antagonism, receptor occupancy profile, and pharmacologic activity. J Clin Psychiatry. 1994 May;55 Suppl:5-12. [PubMed:7520908]
  2. Tuppurainen H, Kuikka JT, Viinamaki H, Husso M, Tiihonen J: Dopamine D2/3 receptor binding potential and occupancy in midbrain and temporal cortex by haloperidol, olanzapine and clozapine. Psychiatry Clin Neurosci. 2009 Aug;63(4):529-37. doi: 10.1111/j.1440-1819.2009.01982.x. Epub 2009 May 22. [PubMed:19496999]
  3. Tadori Y, Forbes RA, McQuade RD, Kikuchi T: Characterization of aripiprazole partial agonist activity at human dopamine D3 receptors. Eur J Pharmacol. 2008 Nov 12;597(1-3):27-33. doi: 10.1016/j.ejphar.2008.09.008. Epub 2008 Sep 20. [PubMed:18831971]
  4. Kessler RM, Ansari MS, Riccardi P, Li R, Jayathilake K, Dawant B, Meltzer HY: Occupancy of striatal and extrastriatal dopamine D2/D3 receptors by olanzapine and haloperidol. Neuropsychopharmacology. 2005 Dec;30(12):2283-9. [PubMed:16123775]
  5. Malmberg, Mikaels, Mohell N: Agonist and inverse agonist activity at the dopamine D3 receptor measured by guanosine 5'--gamma-thio-triphosphate--35S- binding. J Pharmacol Exp Ther. 1998 Apr;285(1):119-26. [PubMed:9536001]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Neuropeptide receptor activity
Specific Function
Receptor for melanin-concentrating hormone, coupled to both G proteins that inhibit adenylyl cyclase and G proteins that activate phosphoinositide hydrolysis.
Gene Name
MCHR1
Uniprot ID
Q99705
Uniprot Name
Melanin-concentrating hormone receptor 1
Molecular Weight
45962.185 Da
References
  1. Theisen FM, Haberhausen M, Firnges MA, Gregory P, Reinders JH, Remschmidt H, Hebebrand J, Antel J: No evidence for binding of clozapine, olanzapine and/or haloperidol to selected receptors involved in body weight regulation. Pharmacogenomics J. 2007 Aug;7(4):275-81. Epub 2006 Sep 19. [PubMed:16983399]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Monoamine transmembrane transporter activity
Specific Function
Involved in the ATP-dependent vesicular transport of biogenic amine neurotransmitters. Pumps cytosolic monoamines including dopamine, norepinephrine, serotonin, and histamine into synaptic vesicles...
Gene Name
SLC18A2
Uniprot ID
Q05940
Uniprot Name
Synaptic vesicular amine transporter
Molecular Weight
55712.075 Da
References
  1. Gonzalez AM, Walther D, Pazos A, Uhl GR: Synaptic vesicular monoamine transporter expression: distribution and pharmacologic profile. Brain Res Mol Brain Res. 1994 Mar;22(1-4):219-26. [PubMed:7912402]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A7
Uniprot ID
P24462
Uniprot Name
Cytochrome P450 3A7
Molecular Weight
57525.03 Da
References
  1. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Curator comments
Data is limited to in vitro studies.
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. Tateishi T, Watanabe M, Kumai T, Tanaka M, Moriya H, Yamaguchi S, Satoh T, Kobayashi S: CYP3A is responsible for N-dealkylation of haloperidol and bromperidol and oxidation of their reduced forms by human liver microsomes. Life Sci. 2000 Nov 3;67(24):2913-20. [PubMed:11133003]
  2. Fang J, McKay G, Song J, Remillrd A, Li X, Midha K: In vitro characterization of the metabolism of haloperidol using recombinant cytochrome p450 enzymes and human liver microsomes. Drug Metab Dispos. 2001 Dec;29(12):1638-43. [PubMed:11717183]
  3. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
Inducer
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Micallef J, Fakra E, Blin O: [Use of antidepressant drugs in schizophrenic patients with depression]. Encephale. 2006 Mar-Apr;32(2 Pt 1):263-9. [PubMed:16910628]
  2. Otani K, Aoshima T: Pharmacogenetics of classical and new antipsychotic drugs. Ther Drug Monit. 2000 Feb;22(1):118-21. [PubMed:10688273]
  3. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  4. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  3. Kalgutkar AS, Taylor TJ, Venkatakrishnan K, Isin EM: Assessment of the contributions of CYP3A4 and CYP3A5 in the metabolism of the antipsychotic agent haloperidol to its potentially neurotoxic pyridinium metabolite and effect of antidepressants on the bioactivation pathway. Drug Metab Dispos. 2003 Mar;31(3):243-9. [PubMed:12584149]
  4. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Prostaglandin-e2 9-reductase activity
Specific Function
NADPH-dependent reductase with broad substrate specificity. Catalyzes the reduction of a wide variety of carbonyl compounds including quinones, prostaglandins, menadione, plus various xenobiotics. ...
Gene Name
CBR1
Uniprot ID
P16152
Uniprot Name
Carbonyl reductase [NADPH] 1
Molecular Weight
30374.73 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Retinoic acid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform has specificity for phenols. Isoform 2 lacks trans...
Gene Name
UGT1A9
Uniprot ID
O60656
Uniprot Name
UDP-glucuronosyltransferase 1-9
Molecular Weight
59940.495 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d 24-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A1
Uniprot ID
P04798
Uniprot Name
Cytochrome P450 1A1
Molecular Weight
58164.815 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Mahar Doan KM, Humphreys JE, Webster LO, Wring SA, Shampine LJ, Serabjit-Singh CJ, Adkison KK, Polli JW: Passive permeability and P-glycoprotein-mediated efflux differentiate central nervous system (CNS) and non-CNS marketed drugs. J Pharmacol Exp Ther. 2002 Dec;303(3):1029-37. [PubMed:12438524]
  2. Nagy H, Goda K, Fenyvesi F, Bacso Z, Szilasi M, Kappelmayer J, Lustyik G, Cianfriglia M, Szabo G Jr: Distinct groups of multidrug resistance modulating agents are distinguished by competition of P-glycoprotein-specific antibodies. Biochem Biophys Res Commun. 2004 Mar 19;315(4):942-9. [PubMed:14985103]
  3. Boulton DW, DeVane CL, Liston HL, Markowitz JS: In vitro P-glycoprotein affinity for atypical and conventional antipsychotics. Life Sci. 2002 May 31;71(2):163-9. [PubMed:12031686]

Drug created on June 13, 2005 07:24 / Updated on September 23, 2018 19:37