Cisapride

Các tên gọi khác (10 ) :

(+-)-Cisapride
4-amino-5-chloro-N-(1-(3-(4-Fluorophenoxy)propyl)-3-methoxypiperidin-4-yl)-2-methoxybenzamide
4-Amino-5-chloro-N-{1-[3-(4-fluoro-phenoxy)-propyl]-3-methoxy-piperidin-4-yl}-2-methoxy-benzamide
cis-4-amino-5-chloro-N-(1-(3-(P-Fluorophenoxy)propyl)-3-methoxy-4-piperidyl)-O-anisamide
cis-4-amino-5-chloro-N-{1-[3-(4-fluorophenoxy)propyl]-3-methoxy-4-piperidinyl}-2-methoxybenzamide
cis-4-amino-5-chloro-N-{1-[3-(P-fluorophenoxy)propyl]-3-methoxy-4-piperidinyl}-O-anisamide
Cisaprid
Cisaprida
Cisapride
Cisapridum

Thuốc đường tiêu hóa

Thuốc Gốc

Small Molecule

CAS: 81098-60-4

ATC: A03FA02

ĐG : Janssen-Ortho Inc. , http://www.janssen-ortho.com

CTHH: C₂₃H₂₉ClFN₃O₄

PTK: 465.945

In many countries (including Canada) cisapride has been either withdrawn or has had its indications limited due to reports about long QT syndrome due to cisapride, which predisposes to arrhythmias. The FDA issued a warning letter regarding this risk to health care professionals and patients.

Nhận Dạng Quốc Tế & Đặc Tính Hóa Học

Công thức hóa học

C₂₃H₂₉ClFN₃O₄

Phân tử khối

465.945

Monoisotopic mass

465.183062343

InChI

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

InChI Key

InChIKey=DCSUBABJRXZOMT-IRLDBZIGSA-N

IUPAC Name

4-amino-5-chloro-N-[(3S,4R)-1-[3-(4-fluorophenoxy)propyl]-3-methoxypiperidin-4-yl]-2-methoxybenzamide

Traditional IUPAC Name

cisapride

SMILES

CO[C@H]1CN(CCCOC2=CC=C(F)C=C2)CC[C@H]1NC(=O)C1=CC(Cl)=C(N)C=C1OC

Độ tan chảy

110 °C

Độ hòa tan

2.71 mg/L

logP

3.3

logS

-4.6

pKa (strongest acidic)

14.58

pKa (Strongest Basic)

8.24

PSA

86.05 Å²

Refractivity

122.93 m³·mol^-1

Polarizability

49.11 Å³

Rotatable Bond Count

H Bond Acceptor Count

H Bond Donor Count

Physiological Charge

Number of Rings

Bioavailability

Rule of Five

true

Ghose Filter

true

MDDR-Like Rule

true

Dược Lực Học : Cisapride is a parasympathomimetic which acts as a serotonin 5-HT₄ agonist. Stimulation of the serotonin receptors increases acetylcholine release in the enteric nervous system. Cisapride stimulates motility of the upper gastrointestinal tract without stimulating gastric, biliary, or pancreatic secretions. Cisapride increases the tone and amplitude of gastric (especially antral) contractions, relaxes the pyloric sphincter and the duodenal bulb, and increases peristalsis of the duodenum and jejunum resulting in accelerated gastric emptying and intestinal transit. It increases the resting tone of the lower esophageal sphincter. It has little, if any, effect on the motility of the colon or gallbladder. Cisapride does not induce muscarinic or nicotinic receptor stimulation, nor does it inhibit acetylcholinesterase activity.

Cơ Chế Tác Dụng : In many countries (including Canada) cisapride has been either withdrawn or has had its indications limited due to reports about long QT syndrome due to cisapride, which predisposes to arrhythmias. The FDA issued a warning letter regarding this risk to health care professionals and patients. Cisapride acts through the stimulation of the serotonin 5-HT₄ receptors which increases acetylcholine release in the enteric nervous system (specifically the myenteric plexus). This results in increased tone and amplitude of gastric (especially antral) contractions, relaxation of the pyloric sphincter and the duodenal bulb, and increased peristalsis of the duodenum and jejunum resulting in accelerated gastric emptying and intestinal transit.

Dược Động Học :

▧ Absorption :
Cisapride is rapidly absorbed after oral administration, with an absolute bioavailability of 35-40%.
▧ Protein binding :
97.5%
▧ Metabolism :
Hepatic. Extensively metabolized via cytochrome P450 3A4 enzyme.
▧ Half Life :
6-12 hours

Chỉ Định : For the symptomatic treatment of adult patients with nocturnal heartburn due to gastroesophageal reflux disease.

Tương Tác Thuốc :

Acenocoumarol Cisapride may increase the anticoagulant effect of acenocoumarol.
Acetophenazine Increased risk of cardiotoxicity and arrhythmias
Alimemazine Increased risk of cardiotoxicity and arrhythmias
Amiodarone Increased risk of cardiotoxicity and arrhythmias
Amitriptyline Increased risk of cardiotoxicity and arrhythmias
Amoxapine Increased risk of cardiotoxicity and arrhythmias
Amprenavir Amprenavir may increase the effect and toxicity of cisapride.
Anisindione Cisapride may increase the anticoagulant effect of anisindione.
Aprepitant Increased risk of cardiotoxicity and arrhythmias
Artemether Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Astemizole Increased risk of cardiotoxicity and arrhythmias
Atazanavir Increased risk of cardiotoxicity and arrhythmias
Bepridil Increased risk of cardiotoxicity and arrhythmias
Boceprevir Boceprevir increases levels by affecting CYP3A4 metabolism. Concomitant therapy is contraindicated.
Bretylium Increased risk of cardiotoxicity and arrhythmias
Chlorpromazine Increased risk of cardiotoxicity and arrhythmias
Clarithromycin Increased risk of cardiotoxicity and arrhythmias
Clomipramine Increased risk of cardiotoxicity and arrhythmias
Crizotinib Concurrent use with drugs that prolong QTc interval is contraindicated.
Delavirdine Delavirdine, a strong CYP3A4 inhibitor, may increase the metabolism of cisapride. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of cisapride if delavirdine is initiated, discontinued or dose changed.
Desipramine Increased risk of cardiotoxicity and arrhythmias
Dicoumarol Cisapride may increase the anticoagulant effect of dicumarol.
Dihydroquinidine barbiturate Increased risk of cardiotoxicity and arrhythmias
Diltiazem Diltiazem, a moderate CYP3A4 inhibitor, may increase the serum concentration of cisapride by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of cisapride if diltiazem is initiated, discontinued or dose changed.
Disopyramide Increased risk of cardiotoxicity and arrhythmias
Doxepin Increased risk of cardiotoxicity and arrhythmias
Efavirenz Increased risk of cardiotoxicity and arrhythmias
Encainide Increased risk of cardiotoxicity and arrhythmias
Erythromycin Increased risk of cardiotoxicity and arrhythmias
Ethopropazine Increased risk of cardiotoxicity and arrhythmias
Fexofenadine Increased risk of cardiotoxicity and arrhythmias
Flecainide Increased risk of cardiotoxicity and arrhythmias
Fluconazole Increased risk of cardiotoxicity and arrhythmias
Fluphenazine Increased risk of cardiotoxicity and arrhythmias
Fosamprenavir Amprenavir increases the effect and toxicity of cisapride
Ibutilide Increased risk of cardiotoxicity and arrhythmias
Imipramine Increased risk of cardiotoxicity and arrhythmias
Indinavir Increased risk of cardiotoxicity and arrhythmias
Itraconazole Increased risk of cardiotoxicity and arrhythmias
Josamycin Increased risk of cardiotoxicity and arrhythmias
Ketoconazole Increased risk of cardiotoxicity and arrhythmias
Lumefantrine Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Maprotiline Increased risk of cardiotoxicity and arrhythmias
Mesoridazine Increased risk of cardiotoxicity and arrhythmias
Methdilazine Increased risk of cardiotoxicity and arrhythmias
Methotrimeprazine Increased risk of cardiotoxicity and arrhythmias
Mibefradil Mibefradil increases levels of cisapride
Nefazodone Nefazodone increases serum levels of cisapride
Nelfinavir Increased risk of cardiotoxicity and arrhythmias
Nifedipine Cisapride may increase the effect and toxicity of nifedipine.
Nortriptyline Increased risk of cardiotoxicity and arrhythmias
Perphenazine Increased risk of cardiotoxicity and arrhythmias
Posaconazole Contraindicated co-administration
Procainamide Increased risk of cardiotoxicity and arrhythmias
Prochlorperazine Increased risk of cardiotoxicity and arrhythmias
Promazine Increased risk of cardiotoxicity and arrhythmias
Promethazine Increased risk of cardiotoxicity and arrhythmias
Propafenone Increased risk of cardiotoxicity and arrhythmias
Propiomazine Increased risk of cardiotoxicity and arrhythmias
Protriptyline Increased risk of cardiotoxicity and arrhythmias
Quinidine Increased risk of cardiotoxicity and arrhythmias
Quinidine barbiturate Increased risk of cardiotoxicity and arrhythmias
Quinupristin This combination presents an increased risk of toxicity
Ritonavir Increased risk of cardiotoxicity and arrhythmias
Saquinavir Increased risk of cardiotoxicity and arrhythmias
Sotalol Increased risk of cardiotoxicity and arrhythmias
Tacrolimus Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution. Cisapride may also increase the concentration of Tacrolimus in the blood.
Telaprevir Telaprevir increases levels by affecting CYP3A4 metabolism. Concomitant therapy is contraindicated.
Telavancin Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Telithromycin Telithromycin may reduce clearance of Cisapride. Concomitant therapy is contraindicated.
Terfenadine Increased risk of cardiotoxicity and arrhythmias
Thiethylperazine Increased risk of cardiotoxicity and arrhythmias
Thioridazine Increased risk of cardiotoxicity and arrhythmias
Thiothixene May cause additive QTc-prolonging effects. Increased risk of ventricular arrhythmias. Consider alternate therapy. Thorough risk:benefit assessment is required prior to co-administration.
Tipranavir Tipranavir, co-administered with Ritonavir, may increase the plasma concentration of Cisapride. Concomitant therapy is contraindicated.
Toremifene Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Trifluoperazine Increased risk of cardiotoxicity and arrhythmias
Triflupromazine Increased risk of cardiotoxicity and arrhythmias
Trimipramine Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Troleandomycin Increased risk of cardiotoxicity and arrhythmias
Voriconazole Voriconazole may increase the serum concentration and toxicity of cisapride likely by decreasing its metabolism. Additive QTc prolongation may also occur. Concomitant therapy is contraindicated.
Vorinostat Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Warfarin Cisapride may increase the anticoagulant effect of warfarin.
Zafirlukast Increased risk of cardiotoxicity and arrhythmias
Ziprasidone Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy should be avoided.
Zuclopenthixol Additive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).

Liều Lượng & Cách Dùng : Suspension - Oral
Tablet - Oral

Dữ Kiện Thương Mại

Nhà Sản Xuất

Công ty :

Sản phẩm biệt dược : Enteropride
Công ty :

Sản phẩm biệt dược : Kinestase
Công ty : Janssen-Ortho

Sản phẩm biệt dược : Prepulsid
Công ty :

Sản phẩm biệt dược : Pridesia
Công ty : Janssen-Ortho

Sản phẩm biệt dược : Propulsid
Công ty : Janssen-Ortho

Sản phẩm biệt dược : Propulsid Quicksolv

Đóng gói

Công ty : Janssen-Ortho Inc.

Website : http://www.janssen-ortho.com
Công ty : Neuman Distributors Inc.
Công ty : Ortho Mcneil Janssen Pharmaceutical Inc.

Website : http://www.ortho-mcneil.com
Công ty : PD-Rx Pharmaceuticals Inc.

Website : http://www.pdrx.com
Công ty : Pharmaceutical Utilization Management Program VA Inc.
Công ty : Sandhills Packaging Inc.

Website : http://www.sandhillspackaging.com

Tài Liệu Tham Khảo Thêm

drugbank

http://www.drugbank.ca/drugs/DB00604

KEGG Compound

http://www.genome.jp/dbget-bin/www_bget?cpd:C06910

KEGG Drug

http://www.genome.jp/dbget-bin/www_bget?drug:D00274

BindingDB

http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=50005836

PharmGKB

http://www.pharmgkb.org/drug/PA449011

Wikipedia

http://en.wikipedia.org/wiki/Cisapride

RxList

http://www.rxlist.com/cgi/generic/cisap.htm

Drugs.com

http://www.drugs.com/mtm/cisapride.html

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