Identification

Name
Melperone
Accession Number
DB09224
Type
Small Molecule
Groups
Investigational
Description

Melperone is an atypical antipsychotic of the butyrophenone chemical class, making it structurally related to the typical antipsychotic haloperidol. Melperone has been used for a span of greater than 30 years in the European Union [5]. It has been well established in the treatment of confusion, anxiety, restlessness (particularly in the elderly) and schizophrenia as It is known to be well-tolerated with an excellent safety profile. Recently, it has been studied as a treatment of psychosis related to Parkinson's disease [5].

Structure
Thumb
Synonyms
Not Available
External IDs
FG 5111 / FG-5111
International/Other Brands
Bunil
Categories
UNII
J8WA3K39B7
CAS number
3575-80-2
Weight
Average: 263.356
Monoisotopic: 263.168542495
Chemical Formula
C16H22FNO
InChI Key
DKMFBWQBDIGMHM-UHFFFAOYSA-N
InChI
InChI=1S/C16H22FNO/c1-13-8-11-18(12-9-13)10-2-3-16(19)14-4-6-15(17)7-5-14/h4-7,13H,2-3,8-12H2,1H3
IUPAC Name
1-(4-fluorophenyl)-4-(4-methylpiperidin-1-yl)butan-1-one
SMILES
CC1CCN(CCCC(=O)C2=CC=C(F)C=C2)CC1

Pharmacology

Indication

For the treatment of schizophrenia, sleep, disorders, agitation and mentally confused states [6, 8, 10].

Pharmacodynamics

Melperone has been demonstrated to produce an antipsychotic effect at doses that cause minimal extrapyramidal symptoms frequently associated with more traditional antipsychotics [6, 8].

Mechanism of action

Melperone demonstrates antagonist activity at D2 dopaminergic and 5HT2A serotonergic receptors [8]. It has a weak affinity to D2 receptors and possesses less risk of inducing dopamine receptor supersensitivity after both acute and chronic administration [L3146]. In addition, the ratio of dopamine D4/D2 occupancy for melperone has been shown to resemble the binding profile of clozapine [9].

TargetActionsOrganism
AD(2) dopamine receptor
antagonist
Human
Absorption

Oral doses are rapidly absorbed (Tmax 1.5–3.0 hours post oral ingestion)[A3145].

Volume of distribution
Not Available
Protein binding

Melperone has a bioavailability of 50-70% [A3145].

Metabolism

Mainly hepatic [11].

Route of elimination

Excreted mainly in the urine, with small amounts of unchanged drug [11].

Half life

Approximately 3-4 hours after oral administration [1]. After intramuscular injection, the half-life has been found to be approximately 6 hours [1].

Clearance
Not Available
Toxicity

An overdose of Melperone may result in cardiac arrhythmias [4].

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
2,5-Dimethoxy-4-ethylamphetamineMelperone may decrease the stimulatory activities of 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of adverse effects can be increased when Melperone is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3,4-MethylenedioxyamphetamineMelperone may decrease the stimulatory activities of 3,4-Methylenedioxyamphetamine.
3,5-DinitrocatecholThe therapeutic efficacy of 3,5-Dinitrocatechol can be decreased when used in combination with Melperone.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of adverse effects can be increased when 4-Bromo-2,5-dimethoxyamphetamine is combined with Melperone.
4-MethoxyamphetamineThe risk or severity of adverse effects can be increased when 4-Methoxyamphetamine is combined with Melperone.
5-methoxy-N,N-dimethyltryptamineThe risk or severity of adverse effects can be increased when Melperone is combined with 5-methoxy-N,N-dimethyltryptamine.
7-NitroindazoleThe risk or severity of adverse effects can be increased when 7-Nitroindazole is combined with Melperone.
AbacavirAbacavir may decrease the excretion rate of Melperone which could result in a higher serum level.
AbexinostatThe risk or severity of QTc prolongation can be increased when Melperone is combined with Abexinostat.
Food Interactions
Not Available

References

General References
  1. Borgstrom L, Larsson H, Molander L: Pharmacokinetics of parenteral and oral melperone in man. Eur J Clin Pharmacol. 1982;23(2):173-6. [PubMed:7140807]
  2. Sumiyoshi T, Jayathilake K, Meltzer HY: A comparison of two doses of melperone, an atypical antipsychotic drug, in the treatment of schizophrenia. Schizophr Res. 2003 Jul 1;62(1-2):65-72. [PubMed:12765745]
  3. Hui WK, Mitchell LB, Kavanagh KM, Gillis AM, Wyse DG, Manyari DE, Duff HJ: Melperone: electrophysiologic and antiarrhythmic activity in humans. J Cardiovasc Pharmacol. 1990 Jan;15(1):144-9. [PubMed:1688972]
  4. Koppel, J et al. (1988). Gas chromatographic- mass spectrometric study of urinary metabolism of melperone. Journal of Biomedical Chromatography.
  5. Melperone (an Anti-Psychotic) in Patients With Psychosis Associated With Parkinson's Disease [Link]
  6. The effect of melperone, an atypical antipsychotic drug, on cognitive function in schizophrenia [Link]
  7. Melperone MSDS [Link]
  8. Melperone in Treatment-Refractory Schizophrenia: A Case Series [Link]
  9. Melperone in Treatment-Refractory Schizophrenia: A Case Series [Link]
  10. Melperone [Link]
  11. Quantification of selected antidepressants and antipsychotics in clinical samples using chromatographic methods combined with mass spectrometry: A review (2006-2015) [Link]
  12. Pharmacological data of the atypical neuroleptic compound melperone (Buronil) [Link]
  13. Development of orally disintegrating tablets comprising controlled-release multiparticulate beads [Link]
External Links
KEGG Drug
D07309
PubChem Compound
15387
PubChem Substance
310265130
ChemSpider
14646
BindingDB
81771
ChEBI
93626
ChEMBL
CHEMBL1531134
Wikipedia
Melperone
ATC Codes
N05AD03 — Melperone

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3TerminatedTreatmentAnxiety Disorders / Dementias / Depression / Psychosomatic Disorders / Schizophrenic Disorders1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)78-82[L1318]
boiling point (°C)120-125[L1318]
Predicted Properties
PropertyValueSource
Water Solubility0.049 mg/mLALOGPS
logP3.89ALOGPS
logP3.23ChemAxon
logS-3.7ALOGPS
pKa (Strongest Acidic)16.4ChemAxon
pKa (Strongest Basic)8.9ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area20.31 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity76.25 m3·mol-1ChemAxon
Polarizability30.25 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
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
MS/MS Spectrum - , positiveLC-MS/MSsplash10-02t9-1970000000-6679994e650d6735e617
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0300-0940000000-5f2b3e89368f333f4076

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
Phenylbutylamines / Butyrophenones / Benzoyl derivatives / Aryl alkyl ketones / Fluorobenzenes / Piperidines / Gamma-amino ketones / Aryl fluorides / Trialkylamines / Azacyclic compounds
show 4 more
Substituents
Alkyl-phenylketone / Butyrophenone / Phenylbutylamine / Benzoyl / Aryl alkyl ketone / Fluorobenzene / Halobenzene / Aryl fluoride / Aryl halide / Monocyclic benzene moiety
show 16 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
Not Available

Targets

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

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
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. Grozinger M, Dragicevic A, Hiemke C, Shams M, Muller MJ, Hartter S: Melperone is an inhibitor of the CYP2D6 catalyzed O-demethylation of venlafaxine. Pharmacopsychiatry. 2003 Jan;36(1):3-6. doi: 10.1055/s-2003-38084. [PubMed:12649767]

Drug created on October 22, 2015 14:15 / Updated on November 02, 2018 07:00