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 2849	190.0 nM [IC50]
Glutamate [NMDA] receptor subunit epsilon 2 13 Target ID: CHEMBL1904 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26912202	Antagonist 2849	47.0 nM [IC50]
Sigma opioid receptor 64 Target ID: CHEMBL3465 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25704012	Agonist 2752	28.27 nM [IC50]
Adrenergic receptor alpha-1 171 Target ID: CHEMBL2094251 Sources: http://www.genome.jp/dbget-bin/www_bget?dr:D08064	Antagonist 2849	100.0 nM [IC50]
Kir3.1/Kir3.2 2 Target ID: CHEMBL3038489 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16123769	Inhibitor 8504	7.01 µM [IC50]
Kir3.1/Kir3.4 2 Target ID: CHEMBL3038488 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16123769	Inhibitor 8504	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 8583	Ifenprodil Approved Use Peripheral vascular disease

C_max

Value	Dose	Analyte	Population
10.13 ng/mL EXPERIMENT https://www.sciencedirect.com/science/article/pii/S2211383513000336	5 mg single, intravenous dose: 5 mg route of administration: Intravenous experiment type: SINGLE co-administered:	IFENPRODIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
19.1 ng/mL EXPERIMENT https://www.sciencedirect.com/science/article/pii/S2211383513000336	10 mg single, intravenous dose: 10 mg route of administration: Intravenous experiment type: SINGLE co-administered:	IFENPRODIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
28.9 ng/mL EXPERIMENT https://www.sciencedirect.com/science/article/pii/S2211383513000336	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:	IFENPRODIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
20.4 ng/mL EXPERIMENT https://www.sciencedirect.com/science/article/pii/S2211383513000336	10 mg 1 times / day steady-state, intravenous dose: 10 mg route of administration: Intravenous experiment type: STEADY-STATE co-administered:	IFENPRODIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Analyte	Population
21.7 ng × h/mL EXPERIMENT https://www.sciencedirect.com/science/article/pii/S2211383513000336	5 mg single, intravenous dose: 5 mg route of administration: Intravenous experiment type: SINGLE co-administered:	IFENPRODIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
41.3 ng × h/mL EXPERIMENT https://www.sciencedirect.com/science/article/pii/S2211383513000336	10 mg single, intravenous dose: 10 mg route of administration: Intravenous experiment type: SINGLE co-administered:	IFENPRODIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
63.1 ng × h/mL EXPERIMENT https://www.sciencedirect.com/science/article/pii/S2211383513000336	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:	IFENPRODIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
47 ng × h/mL EXPERIMENT https://www.sciencedirect.com/science/article/pii/S2211383513000336	10 mg 1 times / day steady-state, intravenous dose: 10 mg route of administration: Intravenous experiment type: STEADY-STATE co-administered:	IFENPRODIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Analyte	Population
3.87 h EXPERIMENT https://www.sciencedirect.com/science/article/pii/S2211383513000336	5 mg single, intravenous dose: 5 mg route of administration: Intravenous experiment type: SINGLE co-administered:	IFENPRODIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
3.61 h EXPERIMENT https://www.sciencedirect.com/science/article/pii/S2211383513000336	10 mg single, intravenous dose: 10 mg route of administration: Intravenous experiment type: SINGLE co-administered:	IFENPRODIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
4.07 h EXPERIMENT https://www.sciencedirect.com/science/article/pii/S2211383513000336	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:	IFENPRODIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
4.25 h EXPERIMENT https://www.sciencedirect.com/science/article/pii/S2211383513000336	10 mg 1 times / day steady-state, intravenous dose: 10 mg route of administration: Intravenous experiment type: STEADY-STATE co-administered:	IFENPRODIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

Doses

Dose	Population	Adverse events
40 mg 3 times / day multiple, oral Highest studied dose Dose: 40 mg, 3 times / day Route: oral Route: multiple Dose: 40 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/30756527/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: FED Sources: https://pubmed.ncbi.nlm.nih.gov/30756527/	Sources: https://pubmed.ncbi.nlm.nih.gov/30756527/

PubMed

Title	Date	PubMed
Chronic ethanol ingestion facilitates N-methyl-D-aspartate receptor function and expression in rat lateral/basolateral amygdala neurons.	2003-12	14534353
NMDA currents and receptor protein are downregulated in the amygdala during maintenance of fear memory.	2003-11-12	14614087
Fyn kinase and NR2B-containing NMDA receptors regulate acute ethanol sensitivity but not ethanol intake or conditioned reward.	2003-11	14634488
Acute dissociation for analyses of NMDA receptor function in cortical neurons during aging.	2003-10-15	12951228
Effect of the NR3 subunit on ethanol inhibition of recombinant NMDA receptors.	2003-10-10	14499953
Postsynaptic contributions to hippocampal network hyperexcitability induced by chronic activity blockade in vivo.	2003-10	14622219
Overexpression of spermidine/spermine N1-acetyltransferase elevates the threshold to pentylenetetrazol-induced seizure activity in transgenic mice.	2003-10	14552906
Effects of NMDA receptor antagonists on acute mu-opioid analgesia in the rat.	2003-09	14592689
The effect of (+/-)-CP-101,606, an NMDA receptor NR2B subunit selective antagonist, in the Morris watermaze.	2003-08-29	12969766
Polyamines in a genetic animal model of paroxysmal dyskinesia.	2003-08-15	12885438
Activation of NMDA receptors in rat dentate gyrus granule cells by spontaneous and evoked transmitter release.	2003-08	12904493
Development and subunit composition of synaptic NMDA receptors in the amygdala: NR2B synapses in the adult central amygdala.	2003-07-30	12890782
Enhanced GABA(A) receptor-mediated activity following activation of NMDA receptors in Cajal-Retzius cells in the developing mouse neocortex.	2003-07-01	12730335
Therapeutic N-methyl-D-aspartate receptor antagonists: will reality meet expectation?	2003-07	14619404
Polyamines contribute to ethanol withdrawal-induced neurotoxicity in rat hippocampal slice cultures through interactions with the NMDA receptor.	2003-07	12878916
Amphetamine-evoked c-fos mRNA expression in the caudate-putamen: the effects of DA and NMDA receptor antagonists vary as a function of neuronal phenotype and environmental context.	2003-07	12807422
Behavioral effects of NMDA receptor agonists and antagonists in combination with nitric oxide-related compounds.	2003-06-20	12818699
Lack of ifenprodil anxiolytic activity after its multiple treatment in chronically ethanol-treated rats.	2003-06-20	12814896
ATP inhibits NMDA receptors after heterologous expression and in cultured hippocampal neurons and attenuates NMDA-mediated neurotoxicity.	2003-06-15	12832522
NR2B and NR2D subunits coassemble in cerebellar Golgi cells to form a distinct NMDA receptor subtype restricted to extrasynaptic sites.	2003-06-15	12832518
N-Methyl-D-aspartate receptors contribute to the maintenance of dopaminergic neurons in rat midbrain slice cultures.	2003-05-01	12686381
NMDA-receptor antagonism via dextromethorphan and ifenprodil modulates graded anxiety test performance of C57BL/6 mice.	2003-05	12799527
Role of the NMDA receptor NR2B subunit in the discriminative stimulus effects of ketamine.	2003-05	12799525
Involvement of voltage- and ligand-gated Ca2+ channels in the neuroexcitatory and synergistic effects of putative uremic neurotoxins.	2003-05	12675852
Expression of behavioral sensitization to ethanol by DBA/2J mice: the role of NMDA and non-NMDA glutamate receptors.	2003-05	12669179
Functional NMDA receptor subtype 2B is expressed in astrocytes after ischemia in vivo and anoxia in vitro.	2003-04-15	12716944
Contribution of NR2B subunits to synaptic transmission in amygdaloid interneurons.	2003-04-01	12684439
PSD-95 regulates NMDA receptors in developing cerebellar granule neurons of the rat.	2003-04-01	12576494
Excitatory synaptic transmission in the lateral and central amygdala.	2003-04	12724149
Lithium-induced inhibition of Src tyrosine kinase in rat cerebral cortical neurons: a role in neuroprotection against N-methyl-D-aspartate receptor-mediated excitotoxicity.	2003-03-13	12633868
Ionotropic glutamate receptors: still a target for neuroprotection in brain ischemia? Insights from in vitro studies.	2003-02	12609492
Excitatory amino acid receptors of the electrosensory system: the NR1/NR2B N-methyl-D-aspartate receptor.	2003-02	12574460
Evidence for functionally distinct synaptic NMDA receptors in ventromedial versus dorsolateral striatum.	2003-01	12522160
Comparison of effect of ethanol on N-methyl-D-aspartate- and GABA-gated currents from acutely dissociated neurons: absence of regional differences in sensitivity to ethanol.	2003-01	12490591
Differential alterations in the expression of NMDA receptor subunits following chronic ethanol treatment in primary cultures of rat cortical and hippocampal neurones.	2003-01	12441166
Ionotropic and metabotropic glutamate receptor mediation of glucocorticoid-induced apoptosis in hippocampal cells and the neuroprotective role of synaptic N-methyl-D-aspartate receptors.	2003	12946705
Studies on neuronal apoptosis in primary forebrain cultures: neuroprotective/anti-apoptotic action of NR2B NMDA antagonists.	2003	12835117
Developmental Pb2+ exposure alters NMDAR subtypes and reduces CREB phosphorylation in the rat brain.	2002-12-15	12480136
Expression of functional NR1/NR2B-type NMDA receptors in neuronally differentiated SK-N-SH human cell line.	2002-12	12492429
Ethanol sensitivity of NMDA receptors.	2002-12	12213224
Radioligand binding studies reveal agmatine is a more selective antagonist for a polyamine-site on the NMDA receptor than arcaine or ifenprodil.	2002-10-11	12363406
Intrathecally administered big dynorphin, a prodynorphin-derived peptide, produces nociceptive behavior through an N-methyl-D-aspartate receptor mechanism.	2002-10-11	12363399
Acamprosate, MK-801, and ifenprodil inhibit neurotoxicity and calcium entry induced by ethanol withdrawal in organotypic slice cultures from neonatal rat hippocampus.	2002-10	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.	2002-10	12357151
Resistance to alcohol withdrawal-induced behaviour in Fyn transgenic mice and its reversal by ifenprodil.	2002-09-30	12399115
Selective NR2B NMDA receptor antagonists are protective against staurosporine-induced apoptosis.	2002-09-27	12323394
Site-selective N-methyl-D-aspartate and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate antagonists produce distinct effects in rats performing complex discriminations.	2002-09	12431422
Differential regulation of synaptic and extra-synaptic NMDA receptors.	2002-09	12195433
Effects of acamprosate and some polyamine site ligands of NMDA receptor on short-term memory in rats.	2002-05-24	12191586
[Effects of 2-(4-benzyl-piperidino)-1-(4-hydroxyphenyl)-1-propanol (ifenprodil) on the cardiovascular system in vivo].	1975-09	1238330

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

NP-120

Preferred Name

English

IFENPRODIL

Official Name

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