Haloperidol decanoateProduct ingredient for Haloperidol

Name
Haloperidol decanoate
Drug Entry
Haloperidol

Haloperidol is a high potency first-generation (typical) antipsychotic and one of the most frequently used antipsychotic medications used worldwide.7 While haloperidol has demonstrated pharmacologic activity at a number of receptors in the brain,10 it exerts its antipsychotic effect through its strong antagonism of the dopamine receptor (mainly D2), particularly within the mesolimbic and mesocortical systems of the brain. Haloperidol is indicated for the treatment of the manifestations of several psychotic disorders including schizophrenia, acute psychosis, Tourette syndrome, and other severe behavioural states.16 It is also used off-label for the management of chorea associated with Huntington's disease and for the treatment of intractable hiccups as it is a potent antiemetic. Dopamine-antagonizing medications such as haloperidol are though to improve psychotic symptoms and states that are caused by an over-production of dopamine, such as schizophrenia, which is theorized to be caused by a hyperdopaminergic state within the limbic system of the brain.9

Use of the first-generation antipsychotics (including haloperidol) is considered highly effective for the management of the "positive" symptoms of schizophrenia including hallucinations, hearing voices, aggression/hostility, disorganized speech, and psychomotor agitation. However, this class of drugs is also limited by the development of movement disorders induced by dopamine-blockade such as drug-induced parkinsonism, akathisia, dystonia, tardive dyskinesia, as well as other side effects including sedation, weight gain, and prolactin changes. While there are limited high-quality studies comparing haloperidol to lower-potency first-generation antipsychotics such as Chlorpromazine, Zuclopenthixol, Fluphenazine, and Methotrimeprazine, haloperidol typically demonstrates the least amount of side effects within this class, but demonstrates a stronger disposition for causing extrapyramidal symptoms (EPS).6,7,8 These other low‐potency antipsychotics are limited by their lower affinity for dopamine receptors, which requires a higher dose to effectively treat symptoms of schizophrenia. In addition, they block many receptors other than the primary target (dopamine receptors), such as cholinergic or histaminergic receptors, resulting in a higher incidence of side effects such as sedation, weight gain, and hypotension.

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

First-generation antipsychotic drugs have largely been replaced with second- and third-generation (atypical) antipsychotics such as Risperidone, Olanzapine, Clozapine, Quetiapine, Aripiprazole, and Ziprasidone. However, haloperidol use remains widespread and is considered the benchmark for comparison in trials of the newer generation antipsychotics.8

The efficacy of haloperidol was first established in controlled trials in the 1960s.5

Accession Number
DBSALT001195
Structure
Synonyms
Not Available
UNII
AC20PJ4101
CAS Number
74050-97-8
Weight
Average: 530.12
Monoisotopic: 529.2759
Chemical Formula
C31H41ClFNO3
InChI Key
GUTXTARXLVFHDK-UHFFFAOYSA-N
InChI
InChI=1S/C31H41ClFNO3/c1-2-3-4-5-6-7-8-11-30(36)37-31(26-14-16-27(32)17-15-26)20-23-34(24-21-31)22-9-10-29(35)25-12-18-28(33)19-13-25/h12-19H,2-11,20-24H2,1H3
IUPAC Name
4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]piperidin-4-yl decanoate
SMILES
CCCCCCCCCC(=O)OC1(CCN(CCCC(=O)C2=CC=C(F)C=C2)CC1)C1=CC=C(Cl)C=C1
ChemSpider
47814
BindingDB
50053408
ChEBI
31664
ChEMBL
CHEMBL1200986
ZINC
ZINC000008214574
Wikipedia
Haloperidol
Predicted Properties
PropertyValueSource
Water Solubility5.72e-05 mg/mLALOGPS
logP7.22ALOGPS
logP7.91Chemaxon
logS-7ALOGPS
pKa (Strongest Acidic)16.4Chemaxon
pKa (Strongest Basic)8.24Chemaxon
Physiological Charge1Chemaxon
Hydrogen Acceptor Count3Chemaxon
Hydrogen Donor Count0Chemaxon
Polar Surface Area46.61 Å2Chemaxon
Rotatable Bond Count16Chemaxon
Refractivity148.58 m3·mol-1Chemaxon
Polarizability60.01 Å3Chemaxon
Number of Rings3Chemaxon
Bioavailability0Chemaxon
Rule of FiveNoChemaxon
Ghose FilterNoChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleYesChemaxon