IFENPRODIL

Details

Stereochemistry	MIXED
Molecular Formula	C21H27NO2
Molecular Weight	325.4446
Optical Activity	UNSPECIFIED
Defined Stereocenters	0 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(C(O)C1=CC=C(O)C=C1)N2CCC(CC3=CC=CC=C3)CC2

InChI

InChIKey=UYNVMODNBIQBMV-UHFFFAOYSA-N

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

HIDE SMILES / InChI

Description
Sources: http://www.mims.com/india/drug/info/ifenprodil?type=full&mtype=generic
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/11554553 http://en.pharmacodia.com/web/drug/1_11124.html

Ifenprodil (marketed under the brands Vadilex; Dilvax; Creocral; Cerocral) is a selective NMDA receptor (glutamate) antagonist. Additionally, ifenprodil inhibits GIRK channels, and interacts with alpha1 adrenergic, serotonin, and sigma receptors. Ifenprodil acts as a vasodilator. Ifenprodil is a medicine available in a number of countries worldwide, but not in US.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Glutamate NMDA receptor; GRIN1/GRIN2B 6 Target ID: CHEMBL1907603 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20692832	Antagonist 2778	190.0 nM [IC50]
Glutamate [NMDA] receptor subunit epsilon 2 13 Target ID: CHEMBL1904 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26912202	Antagonist 2778	47.0 nM [IC50]
Sigma opioid receptor 63 Target ID: CHEMBL3465 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25704012	Agonist 2678	28.27 nM [IC50]
Adrenergic receptor alpha-1 169 Target ID: CHEMBL2094251 Sources: http://www.genome.jp/dbget-bin/www_bget?dr:D08064	Antagonist 2778	100.0 nM [IC50]
Kir3.1/Kir3.2 2 Target ID: CHEMBL3038489 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16123769	Inhibitor 8297	7.01 µM [IC50]
Kir3.1/Kir3.4 2 Target ID: CHEMBL3038488 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16123769	Inhibitor 8297	2.83 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Peripheral vascular disorders 15 Sources: http://www.mims.com/india/drug/info/ifenprodil?type=full&mtype=generic	Primary		Approved 8429	Ifenprodil Approved Use Peripheral vascular disease

PubMed

Title	Date	PubMed
[Effects of 2-(4-benzyl-piperidino)-1-(4-hydroxyphenyl)-1-propanol (ifenprodil) on the cardiovascular system in vivo].	1975 Sep	1238330
Effect of multiple ifenprodil or spermidine treatment on social recognition in rats.	2002	12099406
NR2B selective NMDA receptor antagonists.	2002	11945135
Evidence for sigma-1-like receptors in isolated rat liver mitochondrial membranes.	2002 Apr	11934800
NMDA receptor-mediated currents in rat cerebellar granule and unipolar brush cells.	2002 Apr	11929914
An MCASE approach to the search of a cure for Parkinson's Disease.	2002 Apr 2	11926966
Increase in glutamate-induced neurotoxicity by activated astrocytes involves stimulation of protein kinase C.	2002 Aug	12153475
Spermidine attenuates the inhibitory effect of ethanol on NMDA-induced neurotoxicity.	2002 Aug	12122497
Axonal projection, input and output synapses, and synaptic physiology of Cajal-Retzius cells in the developing rat neocortex.	2002 Aug 15	12177189
Ethanol sensitivity of NMDA receptors.	2002 Dec	12213224
A simple cell line based in vitro test system for N-methyl-D-aspartate (NMDA) receptor ligands.	2002 Jan 15	11741727
Synthesis, in vitro and in vivo pharmacology of a C-11 labeled analog of CP-101,606, (+/-)threo-1-(4-hydroxyphenyl)-2-[4-hydroxy-4-(p-[11C]methoxyphenyl)piperidino]-1-propanol, as a PET tracer for NR2B subunit-containing NMDA receptors.	2002 Jul	12088721
Mapping the binding site of the neuroprotectant ifenprodil on NMDA receptors.	2002 Jul 15	12122058
Ifenprodil and ethanol enhance NMDA receptor-dependent long-term depression.	2002 Jun	12023522
NMDA receptors and L-type voltage-gated calcium channels contribute to long-term potentiation and different components of fear memory formation in the lateral amygdala.	2002 Jun 15	12077219
Characterisation of striatal NMDA receptors involved in the generation of parkinsonian symptoms: intrastriatal microinjection studies in the 6-OHDA-lesioned rat.	2002 May	12112191
Acamprosate has no effect on NMDA-induced toxicity but reduces toxicity induced by spermidine or by changing the medium in organotypic hippocampal slice cultures from rat.	2002 May	12045473
Extrasynaptic NMDARs oppose synaptic NMDARs by triggering CREB shut-off and cell death pathways.	2002 May	11953750
Deletion of the C-terminal domain of the NR2B subunit alters channel properties and synaptic targeting of N-methyl-D-aspartate receptors in nascent neocortical synapses.	2002 May 1	12111856
Developmental profiles of glutamate receptors and synaptic transmission at a single synapse in the mouse auditory brainstem.	2002 May 1	11986375
Subtypes of NMDA receptors in new-born rat hippocampal granule cells.	2002 May 15	12015419
Effects of acamprosate and some polyamine site ligands of NMDA receptor on short-term memory in rats.	2002 May 24	12191586
Acamprosate, MK-801, and ifenprodil inhibit neurotoxicity and calcium entry induced by ethanol withdrawal in organotypic slice cultures from neonatal rat hippocampus.	2002 Oct	12394279
Changes in the effect of isoflurane on N-methyl-D-aspartic acid-gated currents in cultured cerebral cortical neurons with time in culture: evidence for subunit specificity.	2002 Oct	12357151
Radioligand binding studies reveal agmatine is a more selective antagonist for a polyamine-site on the NMDA receptor than arcaine or ifenprodil.	2002 Oct 11	12363406
Intrathecally administered big dynorphin, a prodynorphin-derived peptide, produces nociceptive behavior through an N-methyl-D-aspartate receptor mechanism.	2002 Oct 11	12363399
Site-selective N-methyl-D-aspartate and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate antagonists produce distinct effects in rats performing complex discriminations.	2002 Sep	12431422
Differential regulation of synaptic and extra-synaptic NMDA receptors.	2002 Sep	12195433
Selective NR2B NMDA receptor antagonists are protective against staurosporine-induced apoptosis.	2002 Sep 27	12323394
Excitatory synaptic transmission in the lateral and central amygdala.	2003 Apr	12724149
PSD-95 regulates NMDA receptors in developing cerebellar granule neurons of the rat.	2003 Apr 1	12576494
Functional NMDA receptor subtype 2B is expressed in astrocytes after ischemia in vivo and anoxia in vitro.	2003 Apr 15	12716944
Activation of NMDA receptors in rat dentate gyrus granule cells by spontaneous and evoked transmitter release.	2003 Aug	12904493
The effect of (+/-)-CP-101,606, an NMDA receptor NR2B subunit selective antagonist, in the Morris watermaze.	2003 Aug 29	12969766
Ionotropic glutamate receptors: still a target for neuroprotection in brain ischemia? Insights from in vitro studies.	2003 Feb	12609492
Excitatory amino acid receptors of the electrosensory system: the NR1/NR2B N-methyl-D-aspartate receptor.	2003 Feb	12574460
Therapeutic N-methyl-D-aspartate receptor antagonists: will reality meet expectation?	2003 Jul	14619404
Lack of ifenprodil anxiolytic activity after its multiple treatment in chronically ethanol-treated rats.	2003 Jul-Aug	12814896
NR2B and NR2D subunits coassemble in cerebellar Golgi cells to form a distinct NMDA receptor subtype restricted to extrasynaptic sites.	2003 Jun 15	12832518
Behavioral effects of NMDA receptor agonists and antagonists in combination with nitric oxide-related compounds.	2003 Jun 20	12818699
Lithium-induced inhibition of Src tyrosine kinase in rat cerebral cortical neurons: a role in neuroprotection against N-methyl-D-aspartate receptor-mediated excitotoxicity.	2003 Mar 13	12633868
NMDA-receptor antagonism via dextromethorphan and ifenprodil modulates graded anxiety test performance of C57BL/6 mice.	2003 May	12799527
Role of the NMDA receptor NR2B subunit in the discriminative stimulus effects of ketamine.	2003 May	12799525
Involvement of voltage- and ligand-gated Ca2+ channels in the neuroexcitatory and synergistic effects of putative uremic neurotoxins.	2003 May	12675852
Expression of behavioral sensitization to ethanol by DBA/2J mice: the role of NMDA and non-NMDA glutamate receptors.	2003 May	12669179
N-Methyl-D-aspartate receptors contribute to the maintenance of dopaminergic neurons in rat midbrain slice cultures.	2003 May 1	12686381
Overexpression of spermidine/spermine N1-acetyltransferase elevates the threshold to pentylenetetrazol-induced seizure activity in transgenic mice.	2003 Oct	14552906
Effect of the NR3 subunit on ethanol inhibition of recombinant NMDA receptors.	2003 Oct 10	14499953
Acute dissociation for analyses of NMDA receptor function in cortical neurons during aging.	2003 Oct 15	12951228
Effects of NMDA receptor antagonists on acute mu-opioid analgesia in the rat.	2003 Sep	14592689

Patents

Sample Use Guides

In Vivo Use Guide

Oral Peripheral vascular disease Adult: As tartrate: 40-60 mg daily. Injection Peripheral vascular disease Adult: As tartrate: Up to 15 mg daily by deep IM or slow IV Inj or IV infusion.

Route of Administration: Other

In Vitro Use Guide

Ifenprodil (10 uM) reduced whole-cell NMDA-evoked currents by approximately 80 % in Golgi cells of the rat cerebellum..

Name

Type

Language

IFENPRODIL

Official Name

English

NP-120

Code

English

RC-61-91

Code

English

RC 61-91

Code

English

ifenprodil [INN]

Common Name

English

IFENPRODIL [MI]

Common Name

English

4-BENZYL-.ALPHA.-(P-HYDROXYPHENYL)-.BETA.-METHYL-1-PIPERIDINEETHANOL

Common Name

English

Ifenprodil [WHO-DD]

Common Name

English

Classification Tree Code System Code

WHO-VATC

QC04AX28