Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C23H29ClFN3O4 |
Molecular Weight | 465.945 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 2 / 2 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CO[C@H]1CN(CCCOC2=CC=C(F)C=C2)CC[C@H]1NC(=O)C3=C(OC)C=C(N)C(Cl)=C3
InChI
InChIKey=DCSUBABJRXZOMT-IRLDBZIGSA-N
InChI=1S/C23H29ClFN3O4/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)/t20-,22+/m1/s1
Molecular Formula | C23H29ClFN3O4 |
Molecular Weight | 465.945 |
Charge | 0 |
Count |
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Stereochemistry | ABSOLUTE |
Additional Stereochemistry | No |
Defined Stereocenters | 2 / 2 |
E/Z Centers | 0 |
Optical Activity | UNSPECIFIED |
DescriptionSources: http://www.rxlist.com/propulsid-drug.htmCurator's Comment: description was created based on several sources, including:
https://www.drugs.com/pro/propulsid.html | http://www.marvistavet.com/cisapride.pml
Sources: http://www.rxlist.com/propulsid-drug.htm
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.
CNS Activity
Originator
Sources: https://www.google.com/patents/US4962115
Curator's Comment: # Janssen Pharmaceutica N.V.
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL1875 Sources: http://www.rxlist.com/propulsid-drug.htm |
41.5 nM [Ki] | ||
Target ID: CHEMBL340 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10780971 |
|||
Target ID: CHEMBL5282 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10780971 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Palliative | PROPULSID Approved UseCisapride is indicated for the symptomatic treatment of adult patients with nocturnal heartburn due to gastroesophageal reflux disease. Launch Date1993 |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Dose | Population | Adverse 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... |
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... |
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... |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
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
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
yes [Ki 14 uM] | ||||
yes [Ki 16.1 uM] |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
no | ||||
yes | ||||
yes | ||||
yes | ||||
yes | ||||
yes | ||||
yes | yes (co-administration study) Comment: Ketoconazole resulted in an 8 fold increase and fluconazole more than doubled the AUC of cisapride. Many other DDIs: see https://pubmed.ncbi.nlm.nih.gov/10926350/ Page: 10.0 |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
PubMed
Title | Date | PubMed |
---|---|---|
Treatment of functional dyspepsia with a fixed peppermint oil and caraway oil combination preparation as compared to cisapride. A multicenter, reference-controlled double-blind equivalence study. | 1999 Nov |
|
[Lengthening of the QT-interval in a newborn treated with cisapride]. | 1999 Oct 16 |
|
Isolation of the serotoninergic 5-HT4(e) receptor from human heart and comparative analysis of its pharmacological profile in C6-glial and CHO cell lines. | 2000 Feb |
|
Structure of the human serotonin 5-HT4 receptor gene and cloning of a novel 5-HT4 splice variant. | 2000 Feb |
|
Fluorometric screening for metabolism-based drug--drug interactions. | 2000 Jul-Aug |
|
Efficacy and tolerability of cisapride in children. | 2001 |
|
Drug interaction studies with esomeprazole, the (S)-isomer of omeprazole. | 2001 |
|
[Current indications for cisapride]. | 2001 Apr |
|
Cisapride decreases gastroesophageal reflux in preterm infants. | 2001 Apr |
|
The effect of cisapride on the corrected QT interval and QT dispersion in premature infants. | 2001 Aug |
|
No clinical benefit of adding cisapride to pantoprazole for treatment of gastro-oesophageal reflux disease. | 2001 Aug |
|
Survey of primary care physicians' approach to gastroesophageal reflux disease in elderly patients. | 2001 Aug |
|
[Irritable colon]. | 2001 Aug 20 |
|
Pharmacokinetic/pharmacodynamic assessment of the effects of E4031, cisapride, terfenadine and terodiline on monophasic action potential duration in dog. | 2001 Aug-Sep |
|
Determination of cisapride in pharmaceutical preparations using derivative spectrophotometry. | 2001 Feb |
|
Influence of coadministration of fluoxetine on cisapride pharmacokinetics and QTc intervals in healthy volunteers. | 2001 Feb |
|
[Acid-related disease in the population of two Norwegian municipalities--diagnosis and drug therapy]. | 2001 Feb 20 |
|
Cisapride use in preterms. | 2001 Jan |
|
Inhibition of drug metabolism in human liver microsomes by nizatidine, cimetidine and omeprazole. | 2001 Jan |
|
Possible interaction between cisapride and digoxin. | 2001 Jan |
|
Gastroesophageal reflux disease (GERD): current agents and future perspective. | 2001 Jan |
|
Gastric emptying in diabetic gastroparetic dogs: ffects of SK-951,a novel prokinetic agent. | 2001 Jan |
|
Red wine-cisapride interaction: comparison with grapefruit juice. | 2001 Jul |
|
Cisapride improves gallbladder emptying and bile lipid composition in patients with gallstones. | 2001 Jul |
|
[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 |
|
Drug safety: can simple interventions be effective in a complex world? | 2001 May |
|
Design and evaluation of a two-layer floating tablet for gastric retention using cisapride as a model drug. | 2001 May |
|
The canine Purkinje fiber: an in vitro model system for acquired long QT syndrome and drug-induced arrhythmogenesis. | 2001 May |
|
Transgenic mice overexpressing human KvLQT1 dominant-negative isoform. Part II: Pharmacological profile. | 2001 May |
|
Update on acute colonic pseudo-obstruction. | 2001 Oct |
|
Approaching disturbed sleep in late Parkinson's Disease: first step toward a proposal for a revised UPDRS. | 2001 Oct |
|
QT interval effects of cisapride in the clinical setting. | 2001 Sep-Oct |
Patents
Sample Use Guides
In Vivo Use Guide
Sources: https://www.drugs.com/dosage/propulsid.html
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/6143806
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.
Substance Class |
Chemical
Created
by
admin
on
Edited
Sat Dec 16 17:25:34 GMT 2023
by
admin
on
Sat Dec 16 17:25:34 GMT 2023
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Record UNII |
UVL329170W
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Record Status |
Validated (UNII)
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Record Version |
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WHO-VATC |
QA03FA02
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WHO-ATC |
A03FA02
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NCI_THESAURUS |
C267
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CISAPRIDE
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DTXSID3022825
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5338
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m3585
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UVL329170W
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3571
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100000081525
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D020117
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DB00604
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T-87
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279-689-7
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81098-60-4
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C1210
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SUB07479MIG
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Cisapride
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240
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CHEMBL1729
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METABOLIC ENZYME -> SUBSTRATE | |||
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SALT/SOLVATE -> PARENT | |||
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SOLVATE->ANHYDROUS | |||
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TARGET -> AGONIST | |||
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BINDER->LIGAND |
BINDING
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Related Record | Type | Details | ||
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METABOLITE ACTIVE -> PARENT |
Related Record | Type | Details | ||
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ACTIVE MOIETY |
Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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Biological Half-life | PHARMACOKINETIC |
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