CISAPRIDE MONOHYDRATE

US Previously Marketed

Details

Stereochemistry	RACEMIC
Molecular Formula	C23H29ClFN3O4.H2O
Molecular Weight	483.961
Optical Activity	( + / - )
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

O.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=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
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

Approval Year

Targets

Primary Target	Pharmacology	Potency
Serotonin 4 (5-HT4) receptor 39 Target ID: CHEMBL1875 Sources: http://www.rxlist.com/propulsid-drug.htm	Agonist 2678	41.5 nM [Ki]
Cytochrome P450 3A4 127 Target ID: CHEMBL340 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10780971	Substrate 661
Cytochrome P450 2A6 16 Target ID: CHEMBL5282 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10780971	Substrate 661

Conditions

Condition	Modality	Highest Phase	Product
Gastroesophageal reflux disease 59 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/20767-S011_Propulsid.pdf	Palliative	Withdrawn	PROPULSID Approved Use Cisapride is indicated for the symptomatic treatment of adult patients with nocturnal heartburn due to gastroesophageal reflux disease. Launch Date 1993
Megacolon 3 Sources: https://cdn.ymaws.com/www.aavpt.org/resource/resmgr/imported/cisapride.pdf	Primary	Not Provided 504	Unknown Approved Use Unknown
Constipation 112 Sources: https://cdn.ymaws.com/www.aavpt.org/resource/resmgr/imported/cisapride.pdf	Primary	Not Provided 504	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
7.5 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/pre96/020210_S000_Cisapride_BIOPHARMR.pdf	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 DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/pre96/020210_S000_Cisapride_BIOPHARMR.pdf	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 DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/pre96/020210_S000_Cisapride_BIOPHARMR.pdf	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 DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/pre96/020210_S000_Cisapride_BIOPHARMR.pdf	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 DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/pre96/020210_S000_Cisapride_BIOPHARMR.pdf	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	Analyte	Population
88.1 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/pre96/020210_S000_Cisapride_BIOPHARMR.pdf	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 DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/pre96/020210_S000_Cisapride_BIOPHARMR.pdf	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 DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/pre96/020210_S000_Cisapride_BIOPHARMR.pdf	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 DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/pre96/020210_S000_Cisapride_BIOPHARMR.pdf	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 DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/pre96/020210_S000_Cisapride_BIOPHARMR.pdf	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

T_1/2

Value	Dose	Analyte	Population
8.2 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/pre96/020210_S000_Cisapride_BIOPHARMR.pdf	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 DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/pre96/020210_S000_Cisapride_BIOPHARMR.pdf	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 DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/pre96/020210_S000_Cisapride_BIOPHARMR.pdf	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 DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/pre96/020210_S000_Cisapride_BIOPHARMR.pdf	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 DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/pre96/020210_S000_Cisapride_BIOPHARMR.pdf	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: https://pubmed.ncbi.nlm.nih.gov/9925843/	healthy, newborns n = 1 Health Status: healthy Condition: premature infants, <36 weeks Age Group: newborns Sex: M+F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/9925843/	Other AEs: Arrhythmia... Other AEs: Arrhythmia (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/9925843/
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: https://pubmed.ncbi.nlm.nih.gov/9925843/	healthy, newborns n = 58000 Health Status: healthy Condition: premature infants, <36 weeks Age Group: newborns Sex: M+F Population Size: 58000 Sources: https://pubmed.ncbi.nlm.nih.gov/9925843/	Other AEs: Diarrhea... Other AEs: Diarrhea (12 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/9925843/
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: https://pubmed.ncbi.nlm.nih.gov/9925843/	healthy, newborns n = 2 Health Status: healthy Condition: premature infants, <36 weeks Age Group: newborns Sex: M+F Population Size: 2 Sources: https://pubmed.ncbi.nlm.nih.gov/9925843/	Other AEs: Arrhythmia... Other AEs: Arrhythmia (2 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/9925843/

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: https://pubmed.ncbi.nlm.nih.gov/9925843/	healthy, newborns n = 1 Health Status: healthy Condition: premature infants, <36 weeks Age Group: newborns Sex: M+F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/9925843/
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: https://pubmed.ncbi.nlm.nih.gov/9925843/	healthy, newborns n = 58000 Health Status: healthy Condition: premature infants, <36 weeks Age Group: newborns Sex: M+F Population Size: 58000 Sources: https://pubmed.ncbi.nlm.nih.gov/9925843/
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: https://pubmed.ncbi.nlm.nih.gov/9925843/	healthy, newborns n = 2 Health Status: healthy Condition: premature infants, <36 weeks Age Group: newborns Sex: M+F Population Size: 2 Sources: https://pubmed.ncbi.nlm.nih.gov/9925843/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737		inhibitor 1852 substrate 1217	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1461	P-gp 1537 CYP1A2 1054 CYP2C19 991 CYP2A6 543 CYP2E1 667

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
CYP2D6 1891	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/10859153/	yes [Ki 14 uM]
P-gp 1650	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/12621386/	yes [Ki 16.1 uM]

Drug as victim

Target	Modality	Activity	Clinical evidence
P-gp 1537	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/12621386/	no
CYP1A2 1054	substrate 3367 Sources: https://bpspubs.onlinelibrary.wiley.com/doi/full/10.1038/sj.bjp.0703246	yes
CYP2A6 543	substrate 3367 Sources: https://bpspubs.onlinelibrary.wiley.com/doi/full/10.1038/sj.bjp.0703246	yes
CYP2C19 991	substrate 3367 Sources: https://bpspubs.onlinelibrary.wiley.com/doi/full/10.1038/sj.bjp.0703246	yes
CYP2D6 1217	substrate 3367 Sources: https://bpspubs.onlinelibrary.wiley.com/doi/full/10.1038/sj.bjp.0703246	yes
CYP2E1 667	substrate 3367 Sources: https://bpspubs.onlinelibrary.wiley.com/doi/full/10.1038/sj.bjp.0703246	yes
CYP3A4 1737	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/20767-S011_Propulsid.pdf#page=10;https://bpspubs.onlinelibrary.wiley.com/doi/full/10.1038/sj.bjp.0703246 Page: 10.0	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/ Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/20767-S011_Propulsid.pdf#page=10;https://bpspubs.onlinelibrary.wiley.com/doi/full/10.1038/sj.bjp.0703246 Page: 10.0

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://pubmed.ncbi.nlm.nih.gov/9374794/

Sourcing

Vendor/Aggregator	ID	URL
AK Scientific, Inc. (AKSCI)	3553AH	http://www.aksci.com/item_detail.php?cat=3553AH
Alfa Chemistry	AP260779882-A	https://reagents.alfa-chemistry.com/product/cisapride-cas-260779-88-2-8872.html
Alfa Chemistry	AP260779882-B	https://reagents.alfa-chemistry.com/product/cisapride-monohydrate-cas-260779-88-2-8873.html
Alichem	129009439	http://www.alichem.com/en/products/260779-88-2.html
Aurora Fine Chemicals LLC	A17.904.038	http://online.aurorafinechemicals.com/info?ID=A17.904.038
AvaChem Scientific	2794H	http://www.avachem.com/productSearch.asp?2794H
BOC Sciences	260779-88-2	https://www.bocsci.com/cisapride-hydrate-cas-260779-88-2-item-103946.html
Chemspace	CSSB00020619548	https://chem-space.com/CSSB00020619548
Clearsynth	CS-O-15504	https://www.clearsynth.com/en/CSO15504.html
Glentham Life Sciences	GL0434	http://www.glentham.com/products/product/GL0434/
Lab Network	LN01806108	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01806108
MolPort	MolPort-016-638-372	https://www.molport.com/shop/molecule-link/MolPort-016-638-372
MolPort	MolPort-044-674-489	https://www.molport.com/shop/molecule-link/MolPort-044-674-489
Selleck Chemicals	S4751	http://www.selleckchem.com/products/cisapride.html
Sigma-Aldrich	C4740_SIGMA	https://www.sigmaaldrich.com/catalog/product/sigma/c4740?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Sigma-Aldrich	1134120_USP	https://www.sigmaaldrich.com/catalog/product/usp/1134120?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Smolecule	S567175	https://www.smolecule.com/products/s567175
abcr GmbH	AB511558	http://www.abcr.de/shop/en/AB511558

PubMed

Title	Date	PubMed
Macrophage Fcgamma receptors expression is altered by treatment with dopaminergic drugs.	1999 Mar	10075867
Correction of defective protein trafficking of a mutant HERG potassium channel in human long QT syndrome. Pharmacological and temperature effects.	1999 Oct 29	10531299
Effects of mexiletine on the canine cardiovascular system complicating cisapride overdose: potential utility of mexiletine for the treatment of drug-induced long QT syndrome.	2000 Aug	11001179
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	10683202
Effects of cisapride on ventricular repolarization in children.	2000 Jul	10943965
Evidence for a cardiac ion channel mutation underlying drug-induced QT prolongation and life-threatening arrhythmias.	2000 Jun	10868744
Pharmacological characterization of the human 5-HT(4(d)) receptor splice variant stably expressed in Chinese hamster ovary cells.	2000 Oct	11030734
A structural basis for drug-induced long QT syndrome.	2000 Oct 24	11005845
Efficacy and tolerability of cisapride in children.	2001	11577921
Comparative safety of the different macrolides.	2001	11574199
Does cisapride influence cardiac rhythm? Results of a United States multicenter, double-blind, placebo-controlled pediatric study.	2001 Apr	11396814
Long-Term treatment with cisapride and antibiotics in liver cirrhosis: effect on small intestinal motility, bacterial overgrowth, and liver function.	2001 Apr	11316178
Postoperative ileus: a preventable event (Br J Surg 2000; 87: 1480-93).	2001 Apr	11298634
Electrogastrography: a non-invasive measurement of gastric function.	2001 Apr-Jun	11491049
Effects of 5-HT(4) receptor agonists, cisapride and mosapride citrate on electrocardiogram in anaesthetized rats and guinea-pigs and conscious cats.	2001 Aug	11555327
Gastrointestinal tract cytomegalovirus infection with prolonged vomiting and fever in an immunocompetent child.	2001 Aug	11519392
Stereoselective metabolism of cisapride and enantiomer-enantiomer interaction in human cytochrome P450 enzymes: major role of CYP3A.	2001 Aug	11454912
5HT4(a) and 5-HT4(b) receptors have nearly identical pharmacology and are both expressed in human atrium and ventricle.	2001 Feb	11218067
Effects of 5-HT(4) receptor agonist prokinetic agents on the action potential parameters of isolated rabbit myocardium.	2001 Feb	11174075
Prokinetics reduce bacterial translocation in cirrhosis: will sweeping the gut keep the fluid clean?	2001 Jan	11208746
A randomized, double-blind placebo-controlled trial of the effects of the 5-hydroxytriptamine(4) agonist cisapride on the female urinary bladder.	2001 Jul	11483905
Effects of cisapride on ventricular depolarization-repolarization and arrhythmia markers in infants.	2001 Jul	11474146
Red wine-cisapride interaction: comparison with grapefruit juice.	2001 Jul	11452240
Cisapride improves gallbladder emptying and bile lipid composition in patients with gallstones.	2001 Jul	11446892
Study of the drug-drug interaction between simvastatin and cisapride in man.	2001 Jun	11497338
Effect of cisapride on gastric sensitivity to distension, gastric compliance and duodeno-gastric reflexes in healthy humans.	2001 Jun-Jul	11529652
Drug safety: can simple interventions be effective in a complex world?	2001 May	11501333
The canine Purkinje fiber: an in vitro model system for acquired long QT syndrome and drug-induced arrhythmogenesis.	2001 May	11336111
Transgenic mice overexpressing human KvLQT1 dominant-negative isoform. Part II: Pharmacological profile.	2001 May	11334836
Dyspepsia in primary care: acid suppression as effective as prokinetic therapy. A randomized clinical trial.	2001 Sep	11521984
Treatment of non-ulcer dyspepsia: a meta-analysis of placebo-controlled prospective studies.	2001 Sep	11521983

Patents

Sample Use Guides

In Vivo Use Guide

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

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 [MART.]

Common Name

English

Cisapride monohydrate [WHO-DD]

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