NAV

Bifeprunox

Identification

Generic Name
Bifeprunox
DrugBank Accession Number
DB04888
Background

Bifeprunox is a novel atypical antipsychotic agent which, along with SLV313, aripiprazole and SSR-181507 combines minimal D2 receptor agonism with 5-HT receptor agonism.

Type
Small Molecule
Groups
Investigational
Structure
3D
Similar Structures
Weight
Average: 385.4583
Monoisotopic: 385.179026995
Chemical Formula
C24H23N3O2
Synonyms
  • Bifeprunox
  • Bifeprunoxum
External IDs
  • DU 127090
  • DU-127090
  • DU127090

Pharmacology

Indication

Bifeprunox is being evaluated for the treatment of schizophrenia, psychosis, and Parkinson's disease.

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Contraindications & Blackbox Warnings
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Pharmacodynamics

Bifeprunox is an atypical antipsychotic drug with mixed (agonist/antagonist) receptor activity with the neurotransmitters dopamine (D2/3/4) and serotonin. Bifeprunox differs from first-generation atypical antipsychotics in that it acts as a partial D2 agonist. This property is shared by aripiprazole, a drug already marketed in Europe and the US for treatment of schizophrenia. A placebo-controlled, dose-finding phase II trial in patients with schizophrenia showed that bifeprunox was both efficacious and well tolerated. Importantly, treatment with bifeprunox did not appear to cause some of the side effects seen with other atypicals agents in routine use, such as weight gain, hyperprolactinaemia and cardiotoxicity.

Mechanism of action

In contrast to D2 receptor antagonism, partial D2 agonism is believed to decrease dopamine activity in an overactive dopamine system while simultaneously increasing dopamine activity in regions of the brain where dopaminergic activity is too low. By blocking overstimulated receptors and stimulating underactive ones, partial D2 agonists act as dopamine stabilisers. In common with aripiprazole, bifeprunox also acts as a serotonin, 5-HT1A agonist. This property may contribute to efficacy against the negative symptoms of schizophrenia and reduce the likelihood of extrapyramidal symptoms (EPS).

TargetActionsOrganism
UDopamine D2 receptorNot AvailableHumans
U5-hydroxytryptamine receptor 1ANot AvailableHumans
Absorption

Not Available

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism
Not Available
Route of elimination

Not Available

Half-life

Not Available

Clearance

Not Available

Adverse Effects
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Toxicity

Not Available

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
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interactions in your software
1,2-BenzodiazepineThe risk or severity of adverse effects can be increased when Bifeprunox is combined with 1,2-Benzodiazepine.
AcetazolamideThe risk or severity of adverse effects can be increased when Acetazolamide is combined with Bifeprunox.
AcetophenazineThe risk or severity of adverse effects can be increased when Acetophenazine is combined with Bifeprunox.
AgomelatineThe risk or severity of adverse effects can be increased when Bifeprunox is combined with Agomelatine.
AlfentanilThe risk or severity of adverse effects can be increased when Alfentanil is combined with Bifeprunox.
AlimemazineThe risk or severity of adverse effects can be increased when Alimemazine is combined with Bifeprunox.
AlmotriptanThe risk or severity of adverse effects can be increased when Almotriptan is combined with Bifeprunox.
AlosetronThe risk or severity of adverse effects can be increased when Alosetron is combined with Bifeprunox.
AlprazolamThe risk or severity of adverse effects can be increased when Alprazolam is combined with Bifeprunox.
AlverineThe risk or severity of adverse effects can be increased when Alverine is combined with Bifeprunox.
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Food Interactions
Not Available

Products

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Product Ingredients
IngredientUNIICASInChI Key
Bifeprunox mesylate8F018D8L02350992-13-1ONWKHSGOYGLGPO-UHFFFAOYSA-N

Categories

Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as biphenyls and derivatives. These are organic compounds containing to benzene rings linked together by a C-C bond.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Biphenyls and derivatives
Direct Parent
Biphenyls and derivatives
Alternative Parents
N-arylpiperazines / Benzoxazolones / Benzylamines / Dialkylarylamines / Phenylmethylamines / N-alkylpiperazines / Aralkylamines / Heteroaromatic compounds / Oxazoles / Trialkylamines
show 6 more
Substituents
1,4-diazinane / Amine / Aralkylamine / Aromatic heteropolycyclic compound / Azacycle / Azole / Benzoxazole / Benzoxazolone / Benzylamine / Biphenyl
show 19 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
AP69E83Z79
CAS number
350992-10-8
InChI Key
CYGODHVAJQTCBG-UHFFFAOYSA-N
InChI
InChI=1S/C24H23N3O2/c28-24-25-21-10-5-11-22(23(21)29-24)27-14-12-26(13-15-27)17-18-6-4-9-20(16-18)19-7-2-1-3-8-19/h1-11,16H,12-15,17H2,(H,25,28)
IUPAC Name
7-[4-({[1,1'-biphenyl]-3-yl}methyl)piperazin-1-yl]-2,3-dihydro-1,3-benzoxazol-2-one
SMILES
O=C1NC2=C(O1)C(=CC=C2)N1CCN(CC2=CC(=CC=C2)C2=CC=CC=C2)CC1

References

General References
  1. Newman-Tancredi A, Cussac D, Depoortere R: Neuropharmacological profile of bifeprunox: merits and limitations in comparison with other third-generation antipsychotics. Curr Opin Investig Drugs. 2007 Jul;8(7):539-54. [Article]
  2. Tadori Y, Kitagawa H, Forbes RA, McQuade RD, Stark A, Kikuchi T: Differences in agonist/antagonist properties at human dopamine D(2) receptors between aripiprazole, bifeprunox and SDZ 208-912. Eur J Pharmacol. 2007 Nov 28;574(2-3):103-11. Epub 2007 Aug 10. [Article]
PubChem Compound
208951
PubChem Substance
175426891
ChemSpider
181044
BindingDB
50241119
ChEMBL
CHEMBL218166
ZINC
ZINC000052971454
Wikipedia
Bifeprunox

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3CompletedTreatmentBipolar Disorder (BD)1
3CompletedTreatmentDepression, Bipolar1
3CompletedTreatmentSchizophrenia5
3TerminatedTreatmentPsychosis and Behavioral Disturbances Associated With Dementia of the Alzheimer's Type1
3TerminatedTreatmentSchizophrenia6
2CompletedTreatmentBipolar 1 Disorder1
2CompletedTreatmentBipolar Disorder (BD) / Schizoaffective Disorders / Schizophrenia1
2CompletedTreatmentSchizoaffective Disorders / Schizophrenia2
1CompletedNot AvailableHealthy Subjects (HS)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0197 mg/mLALOGPS
logP4.36ALOGPS
logP4.51Chemaxon
logS-4.3ALOGPS
pKa (Strongest Acidic)9.47Chemaxon
pKa (Strongest Basic)7.75Chemaxon
Physiological Charge1Chemaxon
Hydrogen Acceptor Count4Chemaxon
Hydrogen Donor Count1Chemaxon
Polar Surface Area44.81 Å2Chemaxon
Rotatable Bond Count4Chemaxon
Refractivity116.49 m3·mol-1Chemaxon
Polarizability43.09 Å3Chemaxon
Number of Rings5Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9887
Caco-2 permeable-0.5707
P-glycoprotein substrateSubstrate0.5278
P-glycoprotein inhibitor IInhibitor0.643
P-glycoprotein inhibitor IIInhibitor0.8377
Renal organic cation transporterInhibitor0.5
CYP450 2C9 substrateNon-substrate0.831
CYP450 2D6 substrateNon-substrate0.5751
CYP450 3A4 substrateSubstrate0.6164
CYP450 1A2 substrateInhibitor0.7388
CYP450 2C9 inhibitorInhibitor0.5321
CYP450 2D6 inhibitorNon-inhibitor0.6822
CYP450 2C19 inhibitorInhibitor0.7502
CYP450 3A4 inhibitorInhibitor0.5981
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.9391
Ames testNon AMES toxic0.6195
CarcinogenicityNon-carcinogens0.9333
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.5436 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Strong inhibitor0.6762
hERG inhibition (predictor II)Inhibitor0.5972
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 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

Targets

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Details1. Dopamine D2 receptor
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
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. Auclair AL, Galinier A, Besnard J, Newman-Tancredi A, Depoortere R: Putative antipsychotics with pronounced agonism at serotonin 5-HT1A and partial agonist activity at dopamine D2 receptors disrupt basal PPI of the startle reflex in rats. Psychopharmacology (Berl). 2007 Jul;193(1):45-54. Epub 2007 Mar 29. [Article]
  2. Newman-Tancredi A, Cussac D, Depoortere R: Neuropharmacological profile of bifeprunox: merits and limitations in comparison with other third-generation antipsychotics. Curr Opin Investig Drugs. 2007 Jul;8(7):539-54. [Article]
Details2. 5-hydroxytryptamine receptor 1A
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Serotonin receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances. Ligand binding causes a conformation change that triggers...
Gene Name
HTR1A
Uniprot ID
P08908
Uniprot Name
5-hydroxytryptamine receptor 1A
Molecular Weight
46106.335 Da
References
  1. Bardin L, Kleven MS, Barret-Grevoz C, Depoortere R, Newman-Tancredi A: Antipsychotic-like vs cataleptogenic actions in mice of novel antipsychotics having D2 antagonist and 5-HT1A agonist properties. Neuropsychopharmacology. 2006 Sep;31(9):1869-79. Epub 2005 Oct 19. [Article]
  2. Auclair AL, Galinier A, Besnard J, Newman-Tancredi A, Depoortere R: Putative antipsychotics with pronounced agonism at serotonin 5-HT1A and partial agonist activity at dopamine D2 receptors disrupt basal PPI of the startle reflex in rats. Psychopharmacology (Berl). 2007 Jul;193(1):45-54. Epub 2007 Mar 29. [Article]
  3. Newman-Tancredi A, Cussac D, Depoortere R: Neuropharmacological profile of bifeprunox: merits and limitations in comparison with other third-generation antipsychotics. Curr Opin Investig Drugs. 2007 Jul;8(7):539-54. [Article]

Drug created at October 21, 2007 14:14 / Updated at February 21, 2021 18:51