General
Preferred name
HALOPERIDOL
Synonyms
HALOPERIDOL HYDROCHLORIDE ()
Haloperidol (D4') ()
Haloperidol D4 ()
Haloperidol (hydrochloride) ()
Haldol ()
Aloperidin ()
Serenace ()
Haloperidol (Haldol) ()
HALOPERIDOL LACTATE ()
MCN-JR-1625 ()
Haldol Solutab ()
Haloperidol decanoate impurity, haloperidol- ()
R-1625 ()
Dolpin ()
Dozic ()
Keselen ()
Fortunan ()
NSC-615296 ()
Kentace ()
NSC-170973 ()
Haloperidol ()
Haloperidol Intensol ()
Haloperidol-d4 ()
P&D ID
PD002312
CAS
52-86-8
1511-16-6
1189986-59-1
Tags
natural product
drug
available
Approved by
FDA
First approval
1967
Drug Status
approved
Drug indication
Antipsychotic
Coronavirus Disease 2019 (COVID-19)
Antidyskinetic (in gilles de la tourette's disease)
Schizophrenia
Max Phase
Phase 4
Probe control
Probe control not defined
Orthogonal probes
0
No orthogonal probes found
Similar probes
0
No structurally similar probes found
Structure
P&D probe-likeness score
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
INDICATION
For the treatment of schizophrenia [L2016]; ; For the treatment of acute psychosis in acutely agitated schizophrenic patients with moderately severe to very severe symptoms [L2016]; ; For the treatment of severe behavioral or psychological symptoms of dementia [L2016]; ; For the treatment of delirium in the pediatric intensive care unit [L2016]; ; For the treatment of agitation or delirium [L2016]; ; For agitationâ or delirium in adult patients with no underlying psychiatric illness [L2016]; ; For use as a second-line agent for rescue treatment of chemotherapy-induced nausea/vomiting [L2016]; ; For the treatment of irritability associated with autistic disorder [L2016]; ; For the treatment of tics and vocal utterances associated with Tourette's syndrome [L2016]; ; 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 [L2016]
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% [L1996]. ; ; 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 [FDA label].; ; Serum concentration peaks 0.5 to 4 hours after an oral dose [L1996].
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 [L2028].
DESCRIPTION
Haloperidol is a typical antipsychotic drug.
(GtoPdb)
MOA
Haloperidol inhibits the effects of dopamine and increases its turnover, however, the exact mechanism of action is not fully understood [FDA 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) [L2017]. 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 [A4962].; ; 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 [L2022].; ; Antagonistic activity regulated through dopamine D2 receptors in the chemoreceptive trigger zone (CTZ) of the brain renders its antiemetic activity [L1996]. 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 [L2018].; ; 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 [A4962]. 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 [FDA 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 [DB00734]. This is also consistent with the theory of a lower affinity for D2 receptors for these drugs [L2018]. As mentioned above, haloperidol binds tightly to the dopamine receptor, potentiating the risk of extrapyramidal symptoms [A4962], and therefore should only been used when necessary.
METABOLISM
Its metabolic fate has not been clearly established, it appears that haloperidol is primarily metabolized in the liver [L1996]. ; ; 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 [L1996].; ; 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 [L1996].; ; Haloperidol is a substrate of _CYP3A4_ and an inhibitor, as well as a stimulator, of _CYP2D6_ [L1996].
DESCRIPTION
Standard H3 agonist. Also H4 agonist
(Tocris Bioactive Compound Library)
DESCRIPTION
Dopamine receptor antagonist; antipsychotic
(LOPAC library)
DESCRIPTION
Antagonist, partly D2 selective
(Tocriscreen Total)
[[ p.pathway_name ]]
[[ compound.targets[tid].gene_name ]]
Cell lines
4
Organisms
5
Compound Sets
36
AdooQ Bioactive Compound Library
ChEMBL Approved Drugs
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Concise Guide to Pharmacology 2017/18
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LSP-MoA library (Laboratory of Systems Pharmacology)
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Other bioactive compounds
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ZINC Tool Compounds
[[ a.name ]]
[[ ligand_id ]]
free of charge
External IDs
78
Molecular Weight
375.14
Hydrogen Bond Acceptors
3
Hydrogen Bond Donors
1
Rotatable Bonds
6
Ring Count
3
Aromatic Ring Count
2
cLogP
4.43
TPSA
40.54
Fraction CSP3
0.38
Chiral centers
0.0
Largest ring
6.0
QED
0.76
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Selectivity
D2/D1
Target
Dopamine Receptor
5-HT
dopamine
DRD1, DRD2, DRD3, DRD4, DRD5, GRIN2B, HRH1, HTR1A, HTR1D, HTR2A, HTR2B, HTR7, KCNH1
Pathway
GPCR/G protein
Neuronal Signaling
Neuroscience
Primary Target
Non-selective Dopamine
MOA
Antagonist
Dopamine D2 receptor inverse agonist
Dopamine D3 receptor inverse agonist
ADRA1B antagonist
Dopamine Receptor antagonist
Member status
member
Indication
schizophrenia, Tourette's disorder
Therapeutic Class
Antipsychotic Agents
Antiviral Agents
Source data
