Explore a selection of our essential drug information below, or:
Identification
- Generic Name
- Ifenprodil
- DrugBank Accession Number
- DB08954
- Background
N-methyl-D-aspartate (NMDA) receptors (NMDARs) are members of the ionotropic glutamate receptor family, with key roles in brain development and neurological function.1,2 NMDARs are heterotetramers that typically involve a dimer of dimers of both GluN1 and GluN2A-D subunits, with each subunit itself composed of an N-terminal domain (NTD), a ligand-binding domain (LBD), a transmembrane domain, and a C-terminal cytoplasmic domain. Binding at the LBD of the agonists glycine (or D-serine) to the GluN1 subunits and of glutamate to the GluN2 subunits is a regulatory mechanism for channel activation. In addition, allosteric modulators are known to bind at the NTDs and form another layer of regulation.1,2 One such allosteric regulator is ifenprodil, which was first shown to bind the NMDARs in the 1990s, and specifically to those NMDARs containing the GluN2B subunit.3 Further studies elucidated that ifenprodil binds strongly at the inter-subunit interface of adjacent GluN1 and GluN2B NTDs, where it acts as a non-competitive antagonist.1,2
Although ifenprodil has received considerable interest in its potential neuromodulatory activities in psychiatric conditions, including dependency4 and depression,5 it has also been shown to have an immunomodulatory effect.5,6 In an unbiased screen for compounds capable of reducing cell death induced by infection with the influenza strain H5N1, ifenprodil was found to have a protective effect against H5N1-induced lung damage, in part through its ability to alleviate the H5N1-induced cytokine storm and reduce pulmonary infiltration of neutrophils, natural killer cells, and T cells.6 Ifenprodil is being investigated for its potential utility in treating COVID-19 in an ongoing phase 2b/3 clinical trial (NCT04382924).7
- Type
- Small Molecule
- Groups
- Investigational, Withdrawn
- Structure
Structure for Ifenprodil (DB08954)
- Weight
- Average: 325.4446
Monoisotopic: 325.204179113 - Chemical Formula
- C21H27NO2
- Synonyms
- Ifenprodil
- Ifenprodilum
- External IDs
- RC 61-91
- RC 61-96
Pharmacology
- Indication
Not Available
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Contraindications & Blackbox Warnings
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
Not Available
- Mechanism of action
Target Actions Organism AGlutamate receptor ionotropic, NMDA 2B antagonistHumans AChymotrypsin-like elastase family member 1 inhibitorHumans AGlutamate receptor ionotropic, NMDA 1 antagonistHumans UG protein-activated inward rectifier potassium channel 1 antagonistHumans UG protein-activated inward rectifier potassium channel 2 antagonistHumans UG protein-activated inward rectifier potassium channel 4 antagonistHumans - 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
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
- 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 Ifenprodil is combined with 1,2-Benzodiazepine. Acebutolol Ifenprodil may decrease the antihypertensive activities of Acebutolol. Aceclofenac The risk or severity of hypertension can be increased when Aceclofenac is combined with Ifenprodil. Acemetacin The risk or severity of hypertension can be increased when Ifenprodil is combined with Acemetacin. Acetazolamide The risk or severity of CNS depression can be increased when Acetazolamide is combined with Ifenprodil. - 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 Ifenprodil tartrate 89CTB4XUF7 23210-58-4 DMPRDSPPYMZQBT-CEAXSRTFSA-N - International/Other Brands
- Cerocral (Sanofi) / Furezanil (Tsuruhara Seiyaku) / Iburonol (Towa Yakuhin) / Linbulane (Tatsumi Kagaku) / Technis (Sawai Seiyaku) / Vadilex (Sanofi) / Vasculodil (Kyowa Yakuhin) / Youajyl (Yoshindo)
Categories
- ATC Codes
- C04AX28 — Ifenprodil
- Drug Categories
- Adrenergic Agents
- Adrenergic alpha-Antagonists
- Adrenergic Antagonists
- Agents that produce hypertension
- Anti-Parkinson Drugs
- Anticonvulsants
- Cardiovascular Agents
- Central Nervous System Depressants
- Excitatory Amino Acid Agents
- Excitatory Amino Acid Antagonists
- Experimental Unapproved Treatments for COVID-19
- Neurotransmitter Agents
- NMDA Receptor Antagonists
- Peripheral Vasodilators
- Vasodilating Agents
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as 4-benzylpiperidines. These are organic compounds containing a benzyl group attached to the 4-position of a piperidine.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Piperidines
- Sub Class
- Benzylpiperidines
- Direct Parent
- 4-benzylpiperidines
- Alternative Parents
- Phenylpropanes / Aralkylamines / 1-hydroxy-2-unsubstituted benzenoids / Trialkylamines / Secondary alcohols / 1,2-aminoalcohols / Azacyclic compounds / Organopnictogen compounds / Hydrocarbon derivatives / Aromatic alcohols
- Substituents
- 1,2-aminoalcohol / 1-hydroxy-2-unsubstituted benzenoid / 4-benzylpiperidine / Alcohol / Amine / Aralkylamine / Aromatic alcohol / Aromatic heteromonocyclic compound / Azacycle / Benzenoid
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- R8OE3P6O5S
- CAS number
- 23210-56-2
- InChI Key
- UYNVMODNBIQBMV-UHFFFAOYSA-N
- InChI
- InChI=1S/C21H27NO2/c1-16(21(24)19-7-9-20(23)10-8-19)22-13-11-18(12-14-22)15-17-5-3-2-4-6-17/h2-10,16,18,21,23-24H,11-15H2,1H3
- IUPAC Name
- 4-[2-(4-benzylpiperidin-1-yl)-1-hydroxypropyl]phenol
- SMILES
- CC(C(O)C1=CC=C(O)C=C1)N1CCC(CC2=CC=CC=C2)CC1
References
- Synthesis Reference
U.S. Patent 3,509,164.
- General References
- Tajima N, Karakas E, Grant T, Simorowski N, Diaz-Avalos R, Grigorieff N, Furukawa H: Activation of NMDA receptors and the mechanism of inhibition by ifenprodil. Nature. 2016 Jun 2;534(7605):63-8. doi: 10.1038/nature17679. Epub 2016 May 2. [Article]
- Zhu S, Paoletti P: Allosteric modulators of NMDA receptors: multiple sites and mechanisms. Curr Opin Pharmacol. 2015 Feb;20:14-23. doi: 10.1016/j.coph.2014.10.009. Epub 2014 Nov 12. [Article]
- Williams K: Ifenprodil discriminates subtypes of the N-methyl-D-aspartate receptor: selectivity and mechanisms at recombinant heteromeric receptors. Mol Pharmacol. 1993 Oct;44(4):851-9. [Article]
- Sugaya N, Ogai Y, Aikawa Y, Yumoto Y, Takahama M, Tanaka M, Haraguchi A, Umeno M, Ikeda K: A randomized controlled study of the effect of ifenprodil on alcohol use in patients with alcohol dependence. Neuropsychopharmacol Rep. 2018 Mar;38(1):9-17. doi: 10.1002/npr2.12001. Epub 2018 Feb 18. [Article]
- Yao Y, Ju P, Liu H, Wu X, Niu Z, Zhu Y, Zhang C, Fang Y: Ifenprodil rapidly ameliorates depressive-like behaviors, activates mTOR signaling and modulates proinflammatory cytokines in the hippocampus of CUMS rats. Psychopharmacology (Berl). 2020 May;237(5):1421-1433. doi: 10.1007/s00213-020-05469-0. Epub 2020 Mar 4. [Article]
- Zhang C, Zhang Y, Qin Y, Zhang Q, Liu Q, Shang D, Lu H, Li X, Zhou C, Huang F, Jin N, Jiang C: Ifenprodil and Flavopiridol Identified by Genomewide RNA Interference Screening as Effective Drugs To Ameliorate Murine Acute Lung Injury after Influenza A H5N1 Virus Infection. mSystems. 2019 Dec 10;4(6). pii: 4/6/e00431-19. doi: 10.1128/mSystems.00431-19. [Article]
- Clinical Trial NCT04382924 [Link]
- External Links
- KEGG Drug
- D08064
- PubChem Compound
- 3689
- PubChem Substance
- 310264919
- ChemSpider
- 3561
- BindingDB
- 50083351
- 27403
- ChEBI
- 93829
- ChEMBL
- CHEMBL305187
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Ifenprodil
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 data2 Completed Treatment Idiopathic Pulmonary Fibrosis (IPF) 1 somestatus stop reason just information to hide 2 Not Yet Recruiting Treatment Multiple Sclerosis / Relapsing Remitting Multiple Sclerosis (RRMS) 1 somestatus stop reason just information to hide 2, 3 Completed Treatment Coronavirus Disease 2019 (COVID‑19) / COVID 1 somestatus stop reason just information to hide 1, 2 Completed Treatment Post Traumatic Stress Disorder (PTSD) 1 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 0.105 mg/mL ALOGPS logP 3.98 ALOGPS logP 3.57 Chemaxon logS -3.5 ALOGPS pKa (Strongest Acidic) 9.67 Chemaxon pKa (Strongest Basic) 9.03 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 3 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 43.7 Å2 Chemaxon Rotatable Bond Count 5 Chemaxon Refractivity 98.35 m3·mol-1 Chemaxon Polarizability 37.52 Å3 Chemaxon Number of Rings 3 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
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 175.16255 predictedDeepCCS 1.0 (2019) [M+H]+ 177.52055 predictedDeepCCS 1.0 (2019) [M+Na]+ 184.2339 predictedDeepCCS 1.0 (2019)
Targets
Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Component of NMDA receptor complexes that function as heterotetrameric, ligand-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Channel activation requires binding of the neurotransmitter glutamate to the epsilon subunit, glycine binding to the zeta subunit, plus membrane depolarization to eliminate channel inhibition by Mg(2+) (PubMed:26875626, PubMed:26919761, PubMed:28126851, PubMed:8768735). Sensitivity to glutamate and channel kinetics depend on the subunit composition (PubMed:26875626, PubMed:8768735). In concert with DAPK1 at extrasynaptic sites, acts as a central mediator for stroke damage. Its phosphorylation at Ser-1303 by DAPK1 enhances synaptic NMDA receptor channel activity inducing injurious Ca2+ influx through them, resulting in an irreversible neuronal death. Contributes to neural pattern formation in the developing brain. Plays a role in long-term depression (LTD) of hippocampus membrane currents and in synaptic plasticity (By similarity)
- Specific Function
- amyloid-beta binding
- Gene Name
- GRIN2B
- Uniprot ID
- Q13224
- Uniprot Name
- Glutamate receptor ionotropic, NMDA 2B
- Molecular Weight
- 166365.885 Da
References
- Seppala T, Stromberg C, Mattila MJ: Effects of the novel 5-hydroxytryptamine reuptake inhibitor indalpine and ethanol on psychomotor performance. Arzneimittelforschung. 1988 Jan;38(1):98-102. [Article]
- Tajima N, Karakas E, Grant T, Simorowski N, Diaz-Avalos R, Grigorieff N, Furukawa H: Activation of NMDA receptors and the mechanism of inhibition by ifenprodil. Nature. 2016 Jun 2;534(7605):63-8. doi: 10.1038/nature17679. Epub 2016 May 2. [Article]
- Zhu S, Paoletti P: Allosteric modulators of NMDA receptors: multiple sites and mechanisms. Curr Opin Pharmacol. 2015 Feb;20:14-23. doi: 10.1016/j.coph.2014.10.009. Epub 2014 Nov 12. [Article]
- Williams K: Ifenprodil discriminates subtypes of the N-methyl-D-aspartate receptor: selectivity and mechanisms at recombinant heteromeric receptors. Mol Pharmacol. 1993 Oct;44(4):851-9. [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
- Inhibitor
- General Function
- Serine proteases that hydrolyze many proteins in addition to elastin
- Specific Function
- metal ion binding
- Gene Name
- CELA1
- Uniprot ID
- Q9UNI1
- Uniprot Name
- Chymotrypsin-like elastase family member 1
- Molecular Weight
- 27797.995 Da
References
- 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
- Antagonist
- General Function
- Component of NMDA receptor complexes that function as heterotetrameric, ligand-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Channel activation requires binding of the neurotransmitter glutamate to the epsilon subunit, glycine binding to the zeta subunit, plus membrane depolarization to eliminate channel inhibition by Mg(2+) (PubMed:26875626, PubMed:26919761, PubMed:28105280, PubMed:28126851, PubMed:7685113). Sensitivity to glutamate and channel kinetics depend on the subunit composition (PubMed:26919761)
- Specific Function
- amyloid-beta binding
- Gene Name
- GRIN1
- Uniprot ID
- Q05586
- Uniprot Name
- Glutamate receptor ionotropic, NMDA 1
- Molecular Weight
- 105371.945 Da
References
- Seppala T, Stromberg C, Mattila MJ: Effects of the novel 5-hydroxytryptamine reuptake inhibitor indalpine and ethanol on psychomotor performance. Arzneimittelforschung. 1988 Jan;38(1):98-102. [Article]
- Tajima N, Karakas E, Grant T, Simorowski N, Diaz-Avalos R, Grigorieff N, Furukawa H: Activation of NMDA receptors and the mechanism of inhibition by ifenprodil. Nature. 2016 Jun 2;534(7605):63-8. doi: 10.1038/nature17679. Epub 2016 May 2. [Article]
- Zhu S, Paoletti P: Allosteric modulators of NMDA receptors: multiple sites and mechanisms. Curr Opin Pharmacol. 2015 Feb;20:14-23. doi: 10.1016/j.coph.2014.10.009. Epub 2014 Nov 12. [Article]
- Williams K: Ifenprodil discriminates subtypes of the N-methyl-D-aspartate receptor: selectivity and mechanisms at recombinant heteromeric receptors. Mol Pharmacol. 1993 Oct;44(4):851-9. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Antagonist
- General Function
- This potassium channel is controlled by G proteins. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. This receptor plays a crucial role in regulating the heartbeat
- Specific Function
- G-protein activated inward rectifier potassium channel activity
- Gene Name
- KCNJ3
- Uniprot ID
- P48549
- Uniprot Name
- G protein-activated inward rectifier potassium channel 1
- Molecular Weight
- 56602.84 Da
References
- Kobayashi T, Washiyama K, Ikeda K: Inhibition of G protein-activated inwardly rectifying K+ channels by ifenprodil. Neuropsychopharmacology. 2006 Mar;31(3):516-24. doi: 10.1038/sj.npp.1300844. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Antagonist
- General Function
- This potassium channel may be involved in the regulation of insulin secretion by glucose and/or neurotransmitters acting through G-protein-coupled receptors. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium
- Specific Function
- G-protein activated inward rectifier potassium channel activity
- Gene Name
- KCNJ6
- Uniprot ID
- P48051
- Uniprot Name
- G protein-activated inward rectifier potassium channel 2
- Molecular Weight
- 48450.96 Da
References
- Kobayashi T, Washiyama K, Ikeda K: Inhibition of G protein-activated inwardly rectifying K+ channels by ifenprodil. Neuropsychopharmacology. 2006 Mar;31(3):516-24. doi: 10.1038/sj.npp.1300844. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Antagonist
- General Function
- This potassium channel is controlled by G proteins. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. Can be blocked by external barium
- Specific Function
- G-protein activated inward rectifier potassium channel activity
- Gene Name
- KCNJ5
- Uniprot ID
- P48544
- Uniprot Name
- G protein-activated inward rectifier potassium channel 4
- Molecular Weight
- 47667.3 Da
References
- Kobayashi T, Washiyama K, Ikeda K: Inhibition of G protein-activated inwardly rectifying K+ channels by ifenprodil. Neuropsychopharmacology. 2006 Mar;31(3):516-24. doi: 10.1038/sj.npp.1300844. [Article]
Drug created at May 28, 2014 17:48 / Updated at October 10, 2024 16:48