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Details

Stereochemistry RACEMIC
Molecular Formula C23H29ClFN3O4.H2O
Molecular Weight 483.9616
Optical Activity ( + / - )
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of CISAPRIDE MONOHYDRATE

SMILES

COc1cc(c(cc1C(=N[C@]2([H])CCN(CCCOc3ccc(cc3)F)C[C@]2([H])OC)O)Cl)N.O

InChI

InChIKey=QBYYXIDJOFZORM-LBPAWUGGSA-N
InChI=1S/C23H29ClFN3O4.H2O/c1-30-21-13-19(26)18(24)12-17(21)23(29)27-20-8-10-28(14-22(20)31-2)9-3-11-32-16-6-4-15(25)5-7-16;/h4-7,12-13,20,22H,3,8-11,14,26H2,1-2H3,(H,27,29);1H2/t20-,22+;/m1./s1

HIDE SMILES / InChI

Description
Curator's Comment:: description was created based on several sources, including: https://www.drugs.com/pro/propulsid.html | http://www.marvistavet.com/cisapride.pml

Cisapride is chemically related to metoclopramide, but unlike metoclopramide, it does not cross the blood-brain barrier or have antidopaminergic effects. Cisapride is a serotonin-4 (5-HT4) receptor agonist. Cisapride was indicated for the symptomatic treatment of adult patients with nocturnal heartburn due to gastroesophageal reflux disease. The Food and Drug Administration (FDA) in America stopped the marketing of cisapride as of 14th July 2000. They had received at least 341 reports of heart rhythm abnormalities and these led to 80 deaths. Other reported adverse effects are: headache, diarrhea, abdominal pain, nausea, constipation. Cisapride for animals has been found helpful in some cases of megaesophagus and is a common treatment for feline megacolon. Clarithromycin, erythromycin, and troleandomycin markedly inhibit the metabolism of cisapride. Concurrent administration of certain anticholinergic compounds, such as belladonna alkaloids and dicyclomine, would be expected to compromise the beneficial effects of cisapride.

Originator

Curator's Comment:: # Janssen Pharmaceutica N.V.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
41.5 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Palliative
PROPULSID

Approved Use

Cisapride is indicated for the symptomatic treatment of adult patients with nocturnal heartburn due to gastroesophageal reflux disease.

Launch Date

7.4390399E11
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
7.5 ng/mL
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
NORCISAPRIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
75.7 ng/mL
10 mg 4 times / day steady-state, oral
dose: 10 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
CISAPRIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
115.1 ng/mL
20 mg 4 times / day steady-state, oral
dose: 20 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
CISAPRIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
190.4 ng/mL
40 mg 4 times / day steady-state, oral
dose: 40 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
CISAPRIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
69.5 ng/mL
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
CISAPRIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
88.1 ng × h/mL
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
NORCISAPRIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
1193 ng × h/mL
10 mg 4 times / day steady-state, oral
dose: 10 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
CISAPRIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
1925 ng × h/mL
20 mg 4 times / day steady-state, oral
dose: 20 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
CISAPRIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
2978 ng × h/mL
40 mg 4 times / day steady-state, oral
dose: 40 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
CISAPRIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
719 ng × h/mL
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
CISAPRIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
8.2 h
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
NORCISAPRIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
7.77 h
10 mg 4 times / day steady-state, oral
dose: 10 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
CISAPRIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
8.98 h
20 mg 4 times / day steady-state, oral
dose: 20 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
CISAPRIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
9.76 h
40 mg 4 times / day steady-state, oral
dose: 40 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
CISAPRIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
7.7 h
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
CISAPRIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
0.2 mg/kg 4 times / day steady, oral
Recommended
Dose: 0.2 mg/kg, 4 times / day
Route: oral
Route: steady
Dose: 0.2 mg/kg, 4 times / day
Co-administed with::
erythromycin
Sources:
healthy, newborns
n = 1
Health Status: healthy
Condition: premature infants, <36 weeks
Age Group: newborns
Sex: M+F
Population Size: 1
Sources:
Other AEs: Arrhythmia...
Other AEs:
Arrhythmia (1 patient)
Sources:
0.2 mg/kg 4 times / day steady, oral
Recommended
Dose: 0.2 mg/kg, 4 times / day
Route: oral
Route: steady
Dose: 0.2 mg/kg, 4 times / day
Sources:
healthy, newborns
n = 58000
Health Status: healthy
Condition: premature infants, <36 weeks
Age Group: newborns
Sex: M+F
Population Size: 58000
Sources:
Other AEs: Diarrhea...
Other AEs:
Diarrhea (12 patients)
Sources:
2 mg/kg 4 times / day steady, oral
Studied dose
Dose: 2 mg/kg, 4 times / day
Route: oral
Route: steady
Dose: 2 mg/kg, 4 times / day
Sources:
healthy, newborns
n = 2
Health Status: healthy
Condition: premature infants, <36 weeks
Age Group: newborns
Sex: M+F
Population Size: 2
Sources:
Other AEs: Arrhythmia...
Other AEs:
Arrhythmia (2 patients)
Sources:
AEs

AEs

AESignificanceDosePopulation
Arrhythmia 1 patient
0.2 mg/kg 4 times / day steady, oral
Recommended
Dose: 0.2 mg/kg, 4 times / day
Route: oral
Route: steady
Dose: 0.2 mg/kg, 4 times / day
Co-administed with::
erythromycin
Sources:
healthy, newborns
n = 1
Health Status: healthy
Condition: premature infants, <36 weeks
Age Group: newborns
Sex: M+F
Population Size: 1
Sources:
Diarrhea 12 patients
0.2 mg/kg 4 times / day steady, oral
Recommended
Dose: 0.2 mg/kg, 4 times / day
Route: oral
Route: steady
Dose: 0.2 mg/kg, 4 times / day
Sources:
healthy, newborns
n = 58000
Health Status: healthy
Condition: premature infants, <36 weeks
Age Group: newborns
Sex: M+F
Population Size: 58000
Sources:
Arrhythmia 2 patients
2 mg/kg 4 times / day steady, oral
Studied dose
Dose: 2 mg/kg, 4 times / day
Route: oral
Route: steady
Dose: 2 mg/kg, 4 times / day
Sources:
healthy, newborns
n = 2
Health Status: healthy
Condition: premature infants, <36 weeks
Age Group: newborns
Sex: M+F
Population Size: 2
Sources:
Overview

Overview

OverviewOther

Other InhibitorOther SubstrateOther Inducer






Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
yes [Ki 14 uM]
yes [Ki 16.1 uM]
Drug as victimTox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Fluorometric screening for metabolism-based drug--drug interactions.
2000 Jul-Aug
Drug interaction studies with esomeprazole, the (S)-isomer of omeprazole.
2001
Evaluation of drug-induced QT interval prolongation: implications for drug approval and labelling.
2001
Saquinavir soft gelatin capsule: a comparative safety review.
2001
[The effect of prokinetic treatment and eradication of Helicobacter pylori on gastric emptying and symptoms of functional dyspepsia].
2001
Controversies in the management of chronic constipation.
2001
Drug treatment options for irritable bowel syndrome: managing for success.
2001
Does cisapride influence cardiac rhythm? Results of a United States multicenter, double-blind, placebo-controlled pediatric study.
2001 Apr
Synergistic and antagonistic pharmacodynamic interaction between ranitidine and cisapride: a study on the isolated rabbit intestine.
2001 Apr
Cisapride decreases gastroesophageal reflux in preterm infants.
2001 Apr
Long-Term treatment with cisapride and antibiotics in liver cirrhosis: effect on small intestinal motility, bacterial overgrowth, and liver function.
2001 Apr
Time trends in the coprescribing of cisapride and contraindicated drugs in Umbria, Italy.
2001 Apr 11
Electrogastrography: a non-invasive measurement of gastric function.
2001 Apr-Jun
Enteral feeding in the critically ill: comparison between the supine and prone positions: a prospective crossover study in mechanically ventilated patients.
2001 Aug
A randomised controlled trial of four management strategies for dyspepsia: relationships between symptom subgroups and strategy outcome.
2001 Aug
Survey of primary care physicians' approach to gastroesophageal reflux disease in elderly patients.
2001 Aug
Cisapride does not improve precolonoscopy bowel preparation with either sodium phosphate or polyethylene glycol electrolyte lavage.
2001 Aug
Stereoselective metabolism of cisapride and enantiomer-enantiomer interaction in human cytochrome P450 enzymes: major role of CYP3A.
2001 Aug
Determination of cisapride in pharmaceutical preparations using derivative spectrophotometry.
2001 Feb
5HT4(a) and 5-HT4(b) receptors have nearly identical pharmacology and are both expressed in human atrium and ventricle.
2001 Feb
Ping wei san, a Chinese medicine for gastrointestinal disorders.
2001 Feb
Influence of coadministration of fluoxetine on cisapride pharmacokinetics and QTc intervals in healthy volunteers.
2001 Feb
Alosetron and the rapid component of delayed rectifying potassium current in cardiac cells.
2001 Feb 23
Cisapride use in preterms.
2001 Jan
Inhibition of drug metabolism in human liver microsomes by nizatidine, cimetidine and omeprazole.
2001 Jan
Liquid chromatographic method with electrochemical detection for determination of cisapride in serum.
2001 Jan-Feb
Cisapride plasma levels and corrected QT interval in infants undergoing routine polysomnography.
2001 Jul
Effects of cisapride on ventricular depolarization-repolarization and arrhythmia markers in infants.
2001 Jul
Red wine-cisapride interaction: comparison with grapefruit juice.
2001 Jul
Cisapride improves gallbladder emptying and bile lipid composition in patients with gallstones.
2001 Jul
Pharmacological characterization of a novel 5-HT4 receptor agonist, TS-951, in vitro.
2001 Jul
Pneumatosis intestinalis in a patient with polymyositis.
2001 Jul-Aug
Postmarketing reports of QT prolongation and ventricular arrhythmia in association with cisapride and Food and Drug Administration regulatory actions.
2001 Jun
Gastric emptying in the critically ill.
2001 Jun
Cisapride associated with QTc prolongation in very low birth weight preterm infants.
2001 Jun
"Use-dependent" effects of cisapride on postrest action potentials in rabbit ventricular myocardium.
2001 Jun 22
Discriminative stimulus properties of indorenate in a conditioned taste aversion paradigm.
2001 Mar
Gastroesophageal reflux medications in the treatment of apnea in premature infants.
2001 Mar
[Gynecomastia associated with the simultaneous use of cisapride and lansoprazole].
2001 Mar 24
Contraindicated medications dispensed with cisapride: temporal trends in relation to the sending of 'Dear Doctor' letters.
2001 May
Design and evaluation of a two-layer floating tablet for gastric retention using cisapride as a model drug.
2001 May
Mechanisms of cisapride affecting gallbladder motility.
2001 May
The canine Purkinje fiber: an in vitro model system for acquired long QT syndrome and drug-induced arrhythmogenesis.
2001 May
Review article: erythromycin as a prokinetic agent in infants and children.
2001 May
Cisapride and patient information leaflets.
2001 May 1
Lessons from cisapride.
2001 May 1
Canada needs better drug reporting, says inquest.
2001 May 5
Approaching disturbed sleep in late Parkinson's Disease: first step toward a proposal for a revised UPDRS.
2001 Oct
Dyspepsia in primary care: acid suppression as effective as prokinetic therapy. A randomized clinical trial.
2001 Sep
QT interval effects of cisapride in the clinical setting.
2001 Sep-Oct
Patents

Sample Use Guides

Initiate therapy with one 10 mg tablet or 10 mL of the suspension 4 times daily at least 15 minutes before meals and at bedtime. In some patients the dosage will need to be increased to 20 mg, given as above, to obtain a satisfactory result.
Route of Administration: Oral
In Vitro Use Guide
The addition of Cisapride to the mucosal solution to give a concentration of 6 x 10-5 M caused a transient rise in potential difference (PD, P < 0.05) and short-circuit current (SCC, P < 0.05) with no significant (P > 0.05) change in tissue resistance.
Name Type Language
CISAPRIDE MONOHYDRATE
MI   ORANGE BOOK   WHO-DD  
Common Name English
BENZAMIDE, 4-AMINO-5-CHLORO-N-((3R,4S)-1-(3-(4-FLUOROPHENOXY)PROPYL)-3-METHOXY-4-PIPERIDINYL)-2-METHOXY-, HYDRATE (1:1), REL-
Common Name English
CISAPRIDE MONOHYDRATE [MI]
Common Name English
CISAPRIDE MONOHYDRATE [ORANGE BOOK]
Common Name English
PROPULSID
Brand Name English
CISAPRIDE MONOHYDRATE [WHO-DD]
Common Name English
CISAPRIDE [MART.]
Common Name English
BENZAMIDE, 4-AMINO-5-CHLORO-N-(1-(3-(4-FLUOROPHENOXY)PROPYL)-3-METHOXY-4-PIPERIDINYL)-2-METHOXY-, CIS MONOHYDRATE
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C47794
Created by admin on Sat Jun 26 05:13:05 UTC 2021 , Edited by admin on Sat Jun 26 05:13:05 UTC 2021
Code System Code Type Description
NCI_THESAURUS
C87207
Created by admin on Sat Jun 26 05:13:05 UTC 2021 , Edited by admin on Sat Jun 26 05:13:05 UTC 2021
PRIMARY
EVMPD
SUB01318MIG
Created by admin on Sat Jun 26 05:13:05 UTC 2021 , Edited by admin on Sat Jun 26 05:13:05 UTC 2021
PRIMARY
CAS
260779-88-2
Created by admin on Sat Jun 26 05:13:05 UTC 2021 , Edited by admin on Sat Jun 26 05:13:05 UTC 2021
PRIMARY
ChEMBL
CHEMBL1729
Created by admin on Sat Jun 26 05:13:05 UTC 2021 , Edited by admin on Sat Jun 26 05:13:05 UTC 2021
PRIMARY
PUBCHEM
6917697
Created by admin on Sat Jun 26 05:13:05 UTC 2021 , Edited by admin on Sat Jun 26 05:13:05 UTC 2021
PRIMARY
DRUG BANK
DBSALT001018
Created by admin on Sat Jun 26 05:13:05 UTC 2021 , Edited by admin on Sat Jun 26 05:13:05 UTC 2021
PRIMARY
RXCUI
221077
Created by admin on Sat Jun 26 05:13:05 UTC 2021 , Edited by admin on Sat Jun 26 05:13:05 UTC 2021
PRIMARY RxNorm
FDA UNII
VZV0A4I38W
Created by admin on Sat Jun 26 05:13:05 UTC 2021 , Edited by admin on Sat Jun 26 05:13:05 UTC 2021
PRIMARY
WIKIPEDIA
Cisapride monohydrate
Created by admin on Sat Jun 26 05:13:05 UTC 2021 , Edited by admin on Sat Jun 26 05:13:05 UTC 2021
PRIMARY
MERCK INDEX
M3585
Created by admin on Sat Jun 26 05:13:05 UTC 2021 , Edited by admin on Sat Jun 26 05:13:05 UTC 2021
PRIMARY Merck Index