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.

Reduce drug development failure rates
Build, train, & validate machine-learning models
with evidence-based and structured datasets.
See how
Build, train, & validate predictive machine-learning models with structured datasets.
See how
Contraindications & Blackbox Warnings
Prevent Adverse Drug Events Today
Tap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.
Learn more
Avoid life-threatening adverse drug events with our Clinical API
Learn more
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.

TargetActionsOrganism
USodium-dependent noradrenaline transporterNot AvailableHumans
USodium-dependent serotonin transporterNot AvailableHumans
UDopamine D2 receptorNot AvailableHumans
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 outcomes
With structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!
See the data
Improve decision support & research outcomes with our structured adverse effects data.
See a data sample
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.
DrugInteraction
AbametapirThe serum concentration of Bicifadine can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Bicifadine can be increased when combined with Abatacept.
AbirateroneThe serum concentration of Bicifadine can be increased when it is combined with Abiraterone.
AcebutololThe metabolism of Bicifadine can be decreased when combined with Acebutolol.
AcenocoumarolThe metabolism of Bicifadine can be decreased when combined with Acenocoumarol.
Food Interactions
Not Available

Products

Drug product information from 10+ global regions
Our datasets provide approved product information including:
dosage, form, labeller, route of administration, and marketing period.
Access now
Access drug product information from over 10 global regions.
Access now
Product Ingredients
IngredientUNIICASInChI Key
Bicifadine hydrochlorideOE6G20P68T66504-75-4OTZOPAFTLUOBOM-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
  1. 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]
  2. 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]
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);">
PhaseStatusPurposeConditionsCount
3CompletedTreatmentChronic Lower Back Pain (CLBP)3
2TerminatedTreatmentChronic Peripheral Neuropathy Pain in Diabetics1
2Unknown StatusTreatmentDiabetic 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
PropertyValueSource
Water Solubility0.172 mg/mLALOGPS
logP1.93ALOGPS
logP2.06Chemaxon
logS-3ALOGPS
pKa (Strongest Basic)10.6Chemaxon
Physiological Charge1Chemaxon
Hydrogen Acceptor Count1Chemaxon
Hydrogen Donor Count1Chemaxon
Polar Surface Area12.03 Å2Chemaxon
Rotatable Bond Count1Chemaxon
Refractivity54.31 m3·mol-1Chemaxon
Polarizability20.7 Å3Chemaxon
Number of Rings3Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleYesChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9892
Caco-2 permeable+0.5488
P-glycoprotein substrateSubstrate0.6709
P-glycoprotein inhibitor INon-inhibitor0.9024
P-glycoprotein inhibitor IINon-inhibitor0.8295
Renal organic cation transporterInhibitor0.5272
CYP450 2C9 substrateNon-substrate0.8093
CYP450 2D6 substrateNon-substrate0.7758
CYP450 3A4 substrateNon-substrate0.6496
CYP450 1A2 substrateNon-inhibitor0.7326
CYP450 2C9 inhibitorNon-inhibitor0.8512
CYP450 2D6 inhibitorInhibitor0.6308
CYP450 2C19 inhibitorNon-inhibitor0.7716
CYP450 3A4 inhibitorInhibitor0.5
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.5315
Ames testNon AMES toxic0.6881
CarcinogenicityNon-carcinogens0.8996
BiodegradationNot ready biodegradable0.9418
Rat acute toxicity2.7878 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8583
hERG inhibition (predictor II)Non-inhibitor0.6854
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 GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-059x-5900000000-62b5ff1a0b5771efc7c9
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-00di-1900000000-c109159df11e5a6626c8
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-007o-8900000000-007b83f46386f112b5ec
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-00di-0900000000-8d27bd4f9b1b3f483424
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-00di-0900000000-544be0b46d36218d02e2
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-052f-6900000000-7ea8f5916287c53d2d91
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-05bf-1900000000-7aed69445c2a7365e53d
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-139.11172
predicted
DeepCCS 1.0 (2019)
[M+H]+141.5073
predicted
DeepCCS 1.0 (2019)
[M+Na]+148.95184
predicted
DeepCCS 1.0 (2019)

Targets

Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.
Learn more
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
Learn more
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
  1. 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
  1. 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
  1. 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
  1. 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
  1. 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
  1. 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
  1. 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