Explore a selection of our essential drug information below, or:
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
Structure for Bifeprunox (DB04888)
- 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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Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- 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).
Target Actions Organism A5-hydroxytryptamine receptor 1A modulatorHumans AD(2) dopamine receptor modulatorHumans - 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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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.
Drug Interaction Integrate drug-drug
interactions in your software1,2-Benzodiazepine The risk or severity of CNS depression can be increased when Bifeprunox is combined with 1,2-Benzodiazepine. Acetazolamide The risk or severity of CNS depression can be increased when Acetazolamide is combined with Bifeprunox. Acetophenazine The risk or severity of CNS depression can be increased when Acetophenazine is combined with Bifeprunox. Agomelatine The risk or severity of CNS depression can be increased when Bifeprunox is combined with Agomelatine. Alfentanil The risk or severity of CNS depression can be increased when Alfentanil is combined with Bifeprunox. - Food Interactions
- Not Available
Products
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Ingredient UNII CAS InChI Key Bifeprunox mesylate 8F018D8L02 350992-13-1 ONWKHSGOYGLGPO-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
- 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]
- 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]
- External Links
- PubChem Compound
- 208951
- PubChem Substance
- 175426891
- ChemSpider
- 181044
- BindingDB
- 50241119
- ChEMBL
- CHEMBL218166
- ZINC
- ZINC000052971454
- Wikipedia
- Bifeprunox
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample data3 Completed Treatment Bipolar Disorder (BD) 1 somestatus stop reason just information to hide 3 Completed Treatment Depression, Bipolar 1 somestatus stop reason just information to hide 3 Completed Treatment Schizophrenia 5 somestatus stop reason just information to hide 3 Terminated Treatment Psychosis and Behavioral Disturbances Associated With Dementia of the Alzheimer's Type 1 somestatus stop reason just information to hide 3 Terminated Treatment Schizophrenia 6 somestatus stop reason just information to hide
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
Property Value Source Water Solubility 0.0197 mg/mL ALOGPS logP 4.36 ALOGPS logP 4.51 Chemaxon logS -4.3 ALOGPS pKa (Strongest Acidic) 9.47 Chemaxon pKa (Strongest Basic) 7.75 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 4 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 44.81 Å2 Chemaxon Rotatable Bond Count 4 Chemaxon Refractivity 116.49 m3·mol-1 Chemaxon Polarizability 43.09 Å3 Chemaxon Number of Rings 5 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 1.0 Blood Brain Barrier + 0.9887 Caco-2 permeable - 0.5707 P-glycoprotein substrate Substrate 0.5278 P-glycoprotein inhibitor I Inhibitor 0.643 P-glycoprotein inhibitor II Inhibitor 0.8377 Renal organic cation transporter Inhibitor 0.5 CYP450 2C9 substrate Non-substrate 0.831 CYP450 2D6 substrate Non-substrate 0.5751 CYP450 3A4 substrate Substrate 0.6164 CYP450 1A2 substrate Inhibitor 0.7388 CYP450 2C9 inhibitor Inhibitor 0.5321 CYP450 2D6 inhibitor Non-inhibitor 0.6822 CYP450 2C19 inhibitor Inhibitor 0.7502 CYP450 3A4 inhibitor Inhibitor 0.5981 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.9391 Ames test Non AMES toxic 0.6195 Carcinogenicity Non-carcinogens 0.9333 Biodegradation Not ready biodegradable 1.0 Rat acute toxicity 2.5436 LD50, mol/kg Not applicable hERG inhibition (predictor I) Strong inhibitor 0.6762 hERG inhibition (predictor II) Inhibitor 0.5972
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-000i-0009000000-a3ae22de333a59d3b335 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-000i-0009000000-a1d8d79108deb8644043 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-001i-0009000000-27a9cd6ccd08fca36ce3 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-0cdi-0943000000-c9c11a285004ae39851f Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-05o0-0009000000-51f29845c8186e2c825d Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-0006-6519000000-fbca0dbda9d67a8a773f Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 217.8680575 predictedDarkChem Lite v0.1.0 [M-H]- 188.30383 predictedDeepCCS 1.0 (2019) [M+H]+ 218.6200575 predictedDarkChem Lite v0.1.0 [M+H]+ 190.66183 predictedDeepCCS 1.0 (2019) [M+Na]+ 218.2341575 predictedDarkChem Lite v0.1.0 [M+Na]+ 197.51534 predictedDeepCCS 1.0 (2019)
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Modulator
- General Function
- G-protein coupled receptor for 5-hydroxytryptamine (serotonin) (PubMed:22957663, PubMed:3138543, PubMed:33762731, PubMed:37935376, PubMed:37935377, PubMed:8138923, PubMed:8393041). Also functions as a receptor for various drugs and psychoactive substances (PubMed:22957663, PubMed:3138543, PubMed:33762731, PubMed:38552625, PubMed:8138923, PubMed:8393041). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors, such as adenylate cyclase (PubMed:22957663, PubMed:3138543, PubMed:33762731, PubMed:8138923, PubMed:8393041). HTR1A is coupled to G(i)/G(o) G alpha proteins and mediates inhibitory neurotransmission: signaling inhibits adenylate cyclase activity and activates a phosphatidylinositol-calcium second messenger system that regulates the release of Ca(2+) ions from intracellular stores (PubMed:33762731, PubMed:35610220). Beta-arrestin family members regulate signaling by mediating both receptor desensitization and resensitization processes (PubMed:18476671, PubMed:20363322, PubMed:20945968). Plays a role in the regulation of 5-hydroxytryptamine release and in the regulation of dopamine and 5-hydroxytryptamine metabolism (PubMed:18476671, PubMed:20363322, PubMed:20945968). Plays a role in the regulation of dopamine and 5-hydroxytryptamine levels in the brain, and thereby affects neural activity, mood and behavior (PubMed:18476671, PubMed:20363322, PubMed:20945968). Plays a role in the response to anxiogenic stimuli (PubMed:18476671, PubMed:20363322, PubMed:20945968)
- Specific Function
- G protein-coupled serotonin receptor activity
- Gene Name
- HTR1A
- Uniprot ID
- P08908
- Uniprot Name
- 5-hydroxytryptamine receptor 1A
- Molecular Weight
- 46106.335 Da
References
- 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]
- 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]
- 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]
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Modulator
- General Function
- Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase (PubMed:21645528). Positively regulates postnatal regression of retinal hyaloid vessels via suppression of VEGFR2/KDR activity, downstream of OPN5 (By similarity)
- Specific Function
- dopamine binding
- Gene Name
- DRD2
- Uniprot ID
- P14416
- Uniprot Name
- D(2) dopamine receptor
- Molecular Weight
- 50618.91 Da
References
- 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]
- 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]
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
Drug created at October 21, 2007 14:14 / Updated at August 26, 2024 19:22