Bicifadine
Identification
- Generic Name
- Bicifadine
- DrugBank Accession Number
- DB04889
- Background
Bicifadine (DOV-220075) is a nonopioid analgesic. It is an inhibitor of both the norepinephrine and serotonin transporters and an NMDA antagonist with a non-narcotic profile. Bicifadine was shown to have potent analgesic activity in vivo and was chosen for further development for the treatment of pain.
- Type
- Small Molecule
- Groups
- Investigational
- Structure
- Weight
- Average: 173.2542
Monoisotopic: 173.120449485 - Chemical Formula
- C12H15N
- Synonyms
- Bicifadine
- External IDs
- DOV-220075
Pharmacology
- Indication
For the treatment of pain.
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- Pharmacodynamics
Bicifadine is a chemically distinct molecule with a unique profile of pharmacological activity. Its primary pharmacological action is to enhance and prolong the actions of norepinephrine and serotonin by inhibiting the transport proteins that terminate the physiological actions of the two biogenic amines. Bicifadine is not a narcotic and is well-tolerated and, in preclinical studies, has been shown not to act at any opiate receptor. Bicifadine does not exhibit any anti-inflammatory activity and does not inhibit prostaglandin synthetase in vitro.
- Mechanism of action
Preclinical studies and clinical trials indicate that bicifadine's analgesic properties result through the enhancement and prolongation of norepinephrine and serotonin actions, however other actions may be involved.
Target Actions Organism USodium-dependent noradrenaline transporter Not Available Humans USodium-dependent serotonin transporter Not Available Humans UDopamine D2 receptor Not Available Humans - Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
The primary enzymes responsible for the primary metabolism of bicifadine in humans are MAO-B and CYP2D6.
- Route of elimination
Not Available
- Half-life
Not Available
- Clearance
Not Available
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- 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 softwareAbametapir The serum concentration of Bicifadine can be increased when it is combined with Abametapir. Abatacept The metabolism of Bicifadine can be increased when combined with Abatacept. Abiraterone The serum concentration of Bicifadine can be increased when it is combined with Abiraterone. Acebutolol The metabolism of Bicifadine can be decreased when combined with Acebutolol. Acenocoumarol The metabolism of Bicifadine can be decreased when combined with Acenocoumarol. - Food Interactions
- Not Available
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- Product Ingredients
Ingredient UNII CAS InChI Key Bicifadine hydrochloride OE6G20P68T 66504-75-4 OTZOPAFTLUOBOM-UHFFFAOYSA-N
Categories
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as phenylpiperidines. These are compounds containing a phenylpiperidine skeleton, which consists of a piperidine bound to a phenyl group.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Piperidines
- Sub Class
- Phenylpiperidines
- Direct Parent
- Phenylpiperidines
- Alternative Parents
- Phenylpyrrolidines / Toluenes / Aralkylamines / Pyrroles / Dialkylamines / Azacyclic compounds / Organopnictogen compounds / Hydrocarbon derivatives
- Substituents
- 3-phenylpyrrolidine / Amine / Aralkylamine / Aromatic heteropolycyclic compound / Azacycle / Benzenoid / Hydrocarbon derivative / Monocyclic benzene moiety / Organic nitrogen compound / Organonitrogen compound
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- B0SV3N7J3H
- CAS number
- 71195-57-8
- InChI Key
- OFYVIGTWSQPCLF-UHFFFAOYSA-N
- InChI
- InChI=1S/C12H15N/c1-9-2-4-10(5-3-9)12-6-11(12)7-13-8-12/h2-5,11,13H,6-8H2,1H3
- IUPAC Name
- 1-(4-methylphenyl)-3-azabicyclo[3.1.0]hexane
- SMILES
- CC1=CC=C(C=C1)C12CC1CNC2
References
- General References
- Basile AS, Janowsky A, Golembiowska K, Kowalska M, Tam E, Benveniste M, Popik P, Nikiforuk A, Krawczyk M, Nowak G, Krieter PA, Lippa AS, Skolnick P, Koustova E: Characterization of the antinociceptive actions of bicifadine in models of acute, persistent, and chronic pain. J Pharmacol Exp Ther. 2007 Jun;321(3):1208-25. Epub 2007 Feb 26. [Article]
- Erickson DA, Hollfelder S, Tenge J, Gohdes M, Burkhardt JJ, Krieter PA: In vitro metabolism of the analgesic bicifadine in the mouse, rat, monkey, and human. Drug Metab Dispos. 2007 Dec;35(12):2232-41. Epub 2007 Sep 19. [Article]
- External Links
- KEGG Drug
- D03110
- PubChem Compound
- 47953
- PubChem Substance
- 175426892
- ChemSpider
- 43618
- BindingDB
- 50417944
- ChEMBL
- CHEMBL511099
- Wikipedia
- Bicifadine
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 3 Completed Treatment Chronic Lower Back Pain (CLBP) 3 2 Terminated Treatment Chronic Peripheral Neuropathy Pain in Diabetics 1 2 Unknown Status Treatment Diabetic Peripheral Neuropathy (DPN) 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
Property Value Source Water Solubility 0.172 mg/mL ALOGPS logP 1.93 ALOGPS logP 2.06 Chemaxon logS -3 ALOGPS pKa (Strongest Basic) 10.6 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 1 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 12.03 Å2 Chemaxon Rotatable Bond Count 1 Chemaxon Refractivity 54.31 m3·mol-1 Chemaxon Polarizability 20.7 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule Yes Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 1.0 Blood Brain Barrier + 0.9892 Caco-2 permeable + 0.5488 P-glycoprotein substrate Substrate 0.6709 P-glycoprotein inhibitor I Non-inhibitor 0.9024 P-glycoprotein inhibitor II Non-inhibitor 0.8295 Renal organic cation transporter Inhibitor 0.5272 CYP450 2C9 substrate Non-substrate 0.8093 CYP450 2D6 substrate Non-substrate 0.7758 CYP450 3A4 substrate Non-substrate 0.6496 CYP450 1A2 substrate Non-inhibitor 0.7326 CYP450 2C9 inhibitor Non-inhibitor 0.8512 CYP450 2D6 inhibitor Inhibitor 0.6308 CYP450 2C19 inhibitor Non-inhibitor 0.7716 CYP450 3A4 inhibitor Inhibitor 0.5 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.5315 Ames test Non AMES toxic 0.6881 Carcinogenicity Non-carcinogens 0.8996 Biodegradation Not ready biodegradable 0.9418 Rat acute toxicity 2.7878 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.8583 hERG inhibition (predictor II) Non-inhibitor 0.6854
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS splash10-059x-5900000000-62b5ff1a0b5771efc7c9 Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-00di-1900000000-c109159df11e5a6626c8 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-007o-8900000000-007b83f46386f112b5ec Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-00di-0900000000-8d27bd4f9b1b3f483424 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-00di-0900000000-544be0b46d36218d02e2 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-052f-6900000000-7ea8f5916287c53d2d91 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-05bf-1900000000-7aed69445c2a7365e53d 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]- 139.11172 predictedDeepCCS 1.0 (2019) [M+H]+ 141.5073 predictedDeepCCS 1.0 (2019) [M+Na]+ 148.95184 predictedDeepCCS 1.0 (2019)
Targets
![](https://go.drugbank.com/assets/locked/DrugTargets2-682eb846d210ae4bf33ca03febccfb57bb1c61318e699b729e5df4dfab2c5b67.png)
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Norepinephrine:sodium symporter activity
- Specific Function
- Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals.
- Gene Name
- SLC6A2
- Uniprot ID
- P23975
- Uniprot Name
- Sodium-dependent noradrenaline transporter
- Molecular Weight
- 69331.42 Da
References
- Basile AS, Janowsky A, Golembiowska K, Kowalska M, Tam E, Benveniste M, Popik P, Nikiforuk A, Krawczyk M, Nowak G, Krieter PA, Lippa AS, Skolnick P, Koustova E: Characterization of the antinociceptive actions of bicifadine in models of acute, persistent, and chronic pain. J Pharmacol Exp Ther. 2007 Jun;321(3):1208-25. Epub 2007 Feb 26. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Serotonin:sodium symporter activity
- Specific Function
- Serotonin transporter whose primary function in the central nervous system involves the regulation of serotonergic signaling via transport of serotonin molecules from the synaptic cleft back into t...
- Gene Name
- SLC6A4
- Uniprot ID
- P31645
- Uniprot Name
- Sodium-dependent serotonin transporter
- Molecular Weight
- 70324.165 Da
References
- Basile AS, Janowsky A, Golembiowska K, Kowalska M, Tam E, Benveniste M, Popik P, Nikiforuk A, Krawczyk M, Nowak G, Krieter PA, Lippa AS, Skolnick P, Koustova E: Characterization of the antinociceptive actions of bicifadine in models of acute, persistent, and chronic pain. J Pharmacol Exp Ther. 2007 Jun;321(3):1208-25. Epub 2007 Feb 26. [Article]
- 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
- Basile AS, Janowsky A, Golembiowska K, Kowalska M, Tam E, Benveniste M, Popik P, Nikiforuk A, Krawczyk M, Nowak G, Krieter PA, Lippa AS, Skolnick P, Koustova E: Characterization of the antinociceptive actions of bicifadine in models of acute, persistent, and chronic pain. J Pharmacol Exp Ther. 2007 Jun;321(3):1208-25. Epub 2007 Feb 26. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- 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
- Erickson DA, Hollfelder S, Tenge J, Gohdes M, Burkhardt JJ, Krieter PA: In vitro metabolism of the analgesic bicifadine in the mouse, rat, monkey, and human. Drug Metab Dispos. 2007 Dec;35(12):2232-41. Epub 2007 Sep 19. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Primary amine oxidase activity
- Specific Function
- Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral...
- Gene Name
- MAOB
- Uniprot ID
- P27338
- Uniprot Name
- Amine oxidase [flavin-containing] B
- Molecular Weight
- 58762.475 Da
References
- Erickson DA, Hollfelder S, Tenge J, Gohdes M, Burkhardt JJ, Krieter PA: In vitro metabolism of the analgesic bicifadine in the mouse, rat, monkey, and human. Drug Metab Dispos. 2007 Dec;35(12):2232-41. Epub 2007 Sep 19. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP1A2
- Uniprot ID
- P05177
- Uniprot Name
- Cytochrome P450 1A2
- Molecular Weight
- 58293.76 Da
References
- Erickson DA, Hollfelder S, Tenge J, Gohdes M, Burkhardt JJ, Krieter PA: In vitro metabolism of the analgesic bicifadine in the mouse, rat, monkey, and human. Drug Metab Dispos. 2007 Dec;35(12):2232-41. Epub 2007 Sep 19. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Serotonin binding
- Specific Function
- Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral...
- Gene Name
- MAOA
- Uniprot ID
- P21397
- Uniprot Name
- Amine oxidase [flavin-containing] A
- Molecular Weight
- 59681.27 Da
References
- Erickson DA, Hollfelder S, Tenge J, Gohdes M, Burkhardt JJ, Krieter PA: In vitro metabolism of the analgesic bicifadine in the mouse, rat, monkey, and human. Drug Metab Dispos. 2007 Dec;35(12):2232-41. Epub 2007 Sep 19. [Article]
Drug created at October 21, 2007 16:10 / Updated at November 03, 2023 23:50