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Details

Stereochemistry ACHIRAL
Molecular Formula C17H16N6O.ClH.H2O
Molecular Weight 374.825
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ZONIPORIDE HYDROCHLORIDE MONOHYDRATE

SMILES

O.Cl.NC(=N)NC(=O)C1=C(C2CC2)N(N=C1)C3=C4C=CC=NC4=CC=C3

InChI

InChIKey=UCIJUEGJEFJRMP-UHFFFAOYSA-N
InChI=1S/C17H16N6O.ClH.H2O/c18-17(19)22-16(24)12-9-21-23(15(12)10-6-7-10)14-5-1-4-13-11(14)3-2-8-20-13;;/h1-5,8-10H,6-7H2,(H4,18,19,22,24);1H;1H2

HIDE SMILES / InChI
Molecular Formula ClH
Molecular Weight 36.461
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE
Molecular Formula C17H16N6O
Molecular Weight 320.3485
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE
Molecular Formula H2O
Molecular Weight 18.0153
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/11259552 http://www.abcam.com/zoniporide-hydrochloride-ab142012.html

Zoniporide hydrochloride is a novel, potent and selective NHE-1 inhibitor (IC50 = 14 nM). Reduces infarct size in the isolated heart (EC50 = 0.25 nM). Attenuates post-ischemic cardiac contractile dysfunction and ischemia-reperfusion-induced ventricular fibrillation in vivo. Zoniporide hydrochloride represents a novel class of potent and selective human NHE-1 inhibitors with potential utility for providing cardioprotection in a clinical setting.

Originator

Pfizer
420
Curator's Comment: # Pfizer

Approval Year

Unknown
149124
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
8504
 12000.0 nM [IC50]
Inhibitor
8504
 14.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Phase II
1147
Unknown

Approved Use

Unknown
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
0.07 μg × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/11277524
1 mg/kg single, intravenous
dose: 1 mg/kg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
ZONIPORIDE plasma
Rattus norvegicus
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
0.5 h
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/11277524
1 mg/kg single, intravenous
dose: 1 mg/kg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
ZONIPORIDE plasma
Rattus norvegicus
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
46%
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/11277524
1 mg/kg single, intravenous
dose: 1 mg/kg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
ZONIPORIDE plasma
Rattus norvegicus
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
12 mg/kg 1 times / day multiple, intravenous
Highest studied dose
Dose: 12 mg/kg, 1 times / day
Route: intravenous
Route: multiple
Dose: 12 mg/kg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/16202888
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/16202888
Disc. AE: Elevated liver enzyme levels, Hepatic failure...
Other AEs: Bilirubin elevated, Headache...
AEs leading to
discontinuation/dose reduction:
Elevated liver enzyme levels
Hepatic failure (0.8%)
Vomiting (25.6%)
Other AEs:
Bilirubin elevated
Headache (6.4%)
Atrial fibrillation (6.4%)
Tachycardia (10.9%)
Jaundice (2.3%)
Nausea (41.7%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/16202888
AEs

AEs

AESignificanceDosePopulation
Bilirubin elevated
12 mg/kg 1 times / day multiple, intravenous
Highest studied dose
Dose: 12 mg/kg, 1 times / day
Route: intravenous
Route: multiple
Dose: 12 mg/kg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/16202888
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/16202888
Hepatic failure 0.8%
Disc. AE
12 mg/kg 1 times / day multiple, intravenous
Highest studied dose
Dose: 12 mg/kg, 1 times / day
Route: intravenous
Route: multiple
Dose: 12 mg/kg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/16202888
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/16202888
Tachycardia 10.9%
12 mg/kg 1 times / day multiple, intravenous
Highest studied dose
Dose: 12 mg/kg, 1 times / day
Route: intravenous
Route: multiple
Dose: 12 mg/kg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/16202888
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/16202888
Jaundice 2.3%
12 mg/kg 1 times / day multiple, intravenous
Highest studied dose
Dose: 12 mg/kg, 1 times / day
Route: intravenous
Route: multiple
Dose: 12 mg/kg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/16202888
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/16202888
Vomiting 25.6%
Disc. AE
12 mg/kg 1 times / day multiple, intravenous
Highest studied dose
Dose: 12 mg/kg, 1 times / day
Route: intravenous
Route: multiple
Dose: 12 mg/kg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/16202888
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/16202888
Nausea 41.7%
12 mg/kg 1 times / day multiple, intravenous
Highest studied dose
Dose: 12 mg/kg, 1 times / day
Route: intravenous
Route: multiple
Dose: 12 mg/kg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/16202888
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/16202888
Atrial fibrillation 6.4%
12 mg/kg 1 times / day multiple, intravenous
Highest studied dose
Dose: 12 mg/kg, 1 times / day
Route: intravenous
Route: multiple
Dose: 12 mg/kg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/16202888
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/16202888
Headache 6.4%
12 mg/kg 1 times / day multiple, intravenous
Highest studied dose
Dose: 12 mg/kg, 1 times / day
Route: intravenous
Route: multiple
Dose: 12 mg/kg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/16202888
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/16202888
Elevated liver enzyme levels Disc. AE
12 mg/kg 1 times / day multiple, intravenous
Highest studied dose
Dose: 12 mg/kg, 1 times / day
Route: intravenous
Route: multiple
Dose: 12 mg/kg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/16202888
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/16202888
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG
inhibitor
2252
inhibitor
2438
inhibitor
2507

OverviewOther

Other InhibitorOther SubstrateOther Inducer
P-gp
2052
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
CYP2C9
2497
 no
CYP2D6
2546
 no
CYP3A4
2633
 no
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
P-gp
2052
 no
PubMed

PubMed

TitleDatePubMed
Role of the spinal Na+/H+ exchanger in formalin-induced nociception.
2011-08-21
Critical role of the STAT3 pathway in the cardioprotective efficacy of zoniporide in a model of myocardial preservation - the rat isolated working heart.
2011-02
In vitro-in vivo correlation for intrinsic clearance for drugs metabolized by human aldehyde oxidase.
2010-08
Cross-species comparison of the metabolism and excretion of zoniporide: contribution of aldehyde oxidase to interspecies differences.
2010-04
Paradoxical resistance to myocardial ischemia and age-related cardiomyopathy in NHE1 transgenic mice: a role for ER stress?
2009-02
Effects of KR-33028, a novel Na+/H+ exchanger-1 inhibitor, on glutamate-induced neuronal cell death and ischemia-induced cerebral infarct.
2009-01-12
Neurotoxic effects of zoniporide: a selective inhibitor of the NA+/H+ exchanger isoform 1.
2008-06
Na+/H+ exchanger-1 inhibitors reduce neuronal excitability and alter na+ channel inactivation properties in rat primary sensory neurons.
2008-06
Targeting Na+/H+ exchanger regulation for cardiac protection: a RSKy approach?
2008-04
Does the use of a volatile anesthetic regimen attenuate the incidence of cardiac events after vascular surgery?
2008
Solute diffusion through stripped mouse duodenum.
2007-12
Zoniporide preserves left ventricular compliance during ventricular fibrillation and minimizes postresuscitation myocardial dysfunction through benefits on energy metabolism.
2007-10
The rise of [Na(+)] (i) during ischemia and reperfusion in the rat heart-underlying mechanisms.
2007-09
Initial rate analysis of zoniporide hydrolysis degradants using high-performance liquid chromatography coupled with mass spectrometric detection.
2007
Efficacy of zoniporide, an Na/H exchange ion inhibitor, for reducing perioperative cardiovascular events in vascular surgery patients.
2005-10
Cardioprotective efficacy of zoniporide, a potent and selective inhibitor of Na+/H+ exchanger isoform 1, in an experimental model of cardiopulmonary bypass.
2004-05
Basolateral Na+-H+ exchanger-1 in rat taste receptor cells is involved in neural adaptation to acidic stimuli.
2004-04-01
An overview of inhibitors of Na(+)/H(+) exchanger.
2003-06
Zoniporide: a potent and selective inhibitor of the human sodium-hydrogen exchanger isoform 1 (NHE-1).
2003
Zoniporide: a potent and highly selective inhibitor of human Na(+)/H(+) exchanger-1.
2002-09-06
Apelin, the novel endogenous ligand of the orphan receptor APJ, regulates cardiac contractility.
2002-09-06
A novel sodium-hydrogen exchanger isoform-1 inhibitor, zoniporide, reduces ischemic myocardial injury in vitro and in vivo.
2001-04
Discovery of zoniporide: a potent and selective sodium-hydrogen exchanger type 1 (NHE-1) inhibitor with high aqueous solubility.
2001-03-26
Patents

Patents

06441176
6
06492401
7
06627643
6
06753334
6
06974813
6
JP2003510331A
14
WO2005079803A1
6

Sample Use Guides

In Vivo Use Guide
Rabbits: 0.25, 1, and 4 mg/kg/h, i.v.
Route of Administration: Intravenous
In Vitro Use Guide
Zoniporide inhibited 22Na(+) uptake in fibroblasts expressing human NHE-1 in a concentration-dependent manner (IC(50) = 14 nM)
Substance Class Chemical
Created
by admin
on Mon Mar 31 20:30:40 GMT 2025
Edited
by admin
on Mon Mar 31 20:30:40 GMT 2025
Record UNII
70297XU9ZO
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ZONIPORIDE MONOHYDROCHLORIDE MONOHYDRATE
Preferred Name English
ZONIPORIDE HYDROCHLORIDE MONOHYDRATE
Common Name English
1H-PYRAZOLE-4-CARBOXAMIDE, N-(AMINOIMINOMETHYL)-5-CYCLOPROPYL-1-(5-QUINOLINYL)-, HYDROCHLORIDE, HYDRATE (1:1:1)
Systematic Name English
Code System Code Type Description
PUBCHEM
22267662
Created by admin on Mon Mar 31 20:30:40 GMT 2025 , Edited by admin on Mon Mar 31 20:30:40 GMT 2025
PRIMARY
EPA CompTox
DTXSID80235499
Created by admin on Mon Mar 31 20:30:40 GMT 2025 , Edited by admin on Mon Mar 31 20:30:40 GMT 2025
PRIMARY
FDA UNII
70297XU9ZO
Created by admin on Mon Mar 31 20:30:40 GMT 2025 , Edited by admin on Mon Mar 31 20:30:40 GMT 2025
PRIMARY
CAS
863406-85-3
Created by admin on Mon Mar 31 20:30:40 GMT 2025 , Edited by admin on Mon Mar 31 20:30:40 GMT 2025
PRIMARY
Related Record Type Details
Structure of ZONIPORIDE
PARENT -> SALT/SOLVATE
Structure of ZONIPORIDE HYDROCHLORIDE
ANHYDROUS->SOLVATE
NIH
NCATS
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