Cisapride
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Systematic (IUPAC) name |
(±)-cis-4-amino-5-chloro-N-(1-[3-(4-fluorophenoxy)propyl]-3-methoxypiperidin-4-yl)-2-methoxybenzamide |
Clinical data |
Trade names |
Prepulsid, Propulsid |
AHFS/Drugs.com |
FDA Professional Drug Information |
MedlinePlus |
a694006 |
Pregnancy cat. |
B1 (Australia) |
Legal status |
Unscheduled (AU) POM (UK) ℞-only (US) Schedule 4 (Australia) |
Routes |
oral (tablets), suspension |
Pharmacokinetic data |
Bioavailability |
30-40% |
Protein binding |
97.5% |
Metabolism |
hepatic, intestinal |
Half-life |
10 hours |
Excretion |
renal, biliary |
Identifiers |
CAS number |
81098-60-4 Y |
ATC code |
A03FA02 |
PubChem |
CID 2769 |
IUPHAR ligand |
240 |
DrugBank |
DB00604 |
ChemSpider |
2667 Y |
UNII |
UVL329170W Y |
KEGG |
D00274 Y |
ChEMBL |
CHEMBL1729 N |
Chemical data |
Formula |
C23H29ClFN3O4 |
Mol. mass |
465.945 g/mol |
- Clc1cc(c(OC)cc1N)C(=O)NC3CCN(CCCOc2ccc(F)cc2)CC3OC
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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) Y
Key:DCSUBABJRXZOMT-UHFFFAOYSA-N Y
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N (what is this?) (verify)
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Cisapride is a gastroprokinetic agent, a drug which increases motility in the upper gastrointestinal tract. It acts directly as a serotonin 5-HT4 receptor agonist and indirectly as a parasympathomimetic. Stimulation of the serotonin receptors increases acetylcholine release in the enteric nervous system. It has been sold under the trade names Prepulsid (Janssen-Ortho) and Propulsid (in the U.S.). It was discovered by Janssen Pharmaceutica in 1980. In many countries, it has been either withdrawn from the market or had its indications limited because of side effects.
The commercial preparations of this drug are the racemic mixture of both enantiomers of the compound. The (+) enantiomer itself has the major pharmacologic effects and does not induce many of the detrimental side effects of the mixture.[1]
Clinical uses [edit]
Cisapride increases muscle tone in the esophageal sphincter in people with gastroesophageal reflux disease. It also increases gastric emptying in people with diabetic gastroparesis. It has been used to treat bowel constipation.
In many countries, it has been either withdrawn or had its indications limited because of reports of the side effect long QT syndrome, which predisposes to arrhythmias. The U.S. Food and Drug Administration (FDA) issued a warning letter to doctors,[2] and cisapride was voluntarily removed from the U.S. market on July 14, 2000. However, this evidence remains inconclusive.
Veterinary uses [edit]
Cisapride is still available in the United States for use in animals, and is commonly prescribed by veterinarians to treat megacolon in cats.
Cisapride is also commonly used to treat GI stasis in rabbits, sometimes in conjunction with metoclopramide (Reglan).
Kinetics [edit]
Oral bioavailability of cisapride is approximately 33%. It is primarily inactivated by hepatic metabolism by CYP3A4 with a half life of 10 hours. The dose of the drug should be reduced in case of liver diseases.[3]
Pharmacology and mechanism of action [edit]
As a prokinetic agent that increases gastrointestinal motility, cisapride acts as a selective serotonin agonist in the 5-HT 4 receptor subtype. Cisapride also relieves constipation-like symptoms by indirectly stimulating the release of acetylcholine in the muscarinic receptors.
See also [edit]
References [edit]
Sources [edit]
- Brenner, G. M. (2000). Pharmacology. Philadelphia, PA: W.B. Saunders Company. ISBN 0-7216-7757-6
- Canadian Pharmacists Association (2000). Compendium of Pharmaceuticals and Specialties (25th ed.). Toronto, ON: Webcom. ISBN 0-919115-76-4
- Medline Plus
External links [edit]
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- Agonists: Azapirones: Alnespirone
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- SSR-181,507
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Antagonists: Antipsychotics: Iloperidone
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- Agonists: Lysergamides: Dihydroergotamine
- Methysergide; Triptans: Almotriptan
- Avitriptan
- Eletriptan
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- Bromocriptine
- CP-286,601
- GR-46611
- L-694,247
- L-772,405
- PNU-109,291
- PNU-142633
Antagonists: Lysergamides: Metergoline; Others: Alniditan
- BRL-15,572
- Elzasonan
- GR-127,935
- Ketanserin
- LY-310,762
- LY-367,642
- LY-456,219
- LY-456,220
- Metitepine/Methiothepin
- Ritanserin
- Yohimbine
- Ziprasidone
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- Agonists: Phenethylamines: 2C-B
- 2C-E
- 2C-I
- 2C-T-2
- 2C-T-7
- 2C-T-21
- DOB
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- 5-MeO-DPT
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- α-ET
- α-Methyl-5-HT
- α-MT
- Bufotenin
- DET
- DiPT
- DMT
- DPT
- Psilocin
- Psilocybin; Others: A-372,159
- Bromocriptine
- AL-38022A
- CP-809,101
- Dimemebfe
- Lorcaserin
- Medifoxamine
- MK-212
- Org 12,962
- ORG-37,684
- Oxaflozane
- PNU-22394
- Ro60-0175
- Ro60-0213
- Vabicaserin
- WAY-629
- WAY-161,503
- YM-348
Antagonists: Atypical antipsychotics: Clorotepine
- Clozapine
- Iloperidone
- Melperone
- Olanzapine
- Paliperidone
- Pimozide
- Quetiapine
- Risperidone
- Sertindole
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- Fluoxetine
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- FR-260,010
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- Methysergide
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- RS-102,221
- S-14,671
- SB-200,646
- SB-206,553
- SB-221,284
- SB-228,357
- SB-242,084
- SB-243,213
- SDZ SER-082
- Xylamidine
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- Agonists: Lysergamides: Dihydroergotamine
- Ergotamine
- Lisuride
- LSD
- Mesulergine
- Metergoline
- Methysergide; Tryptamines: 2-Methyl-5-HT
- 5-BT
- 5-CT
- 5-MT
- Bufotenin
- E-6801
- E-6837
- EMD-386,088
- EMDT
- LY-586,713
- N-Methyl-5-HT
- Tryptamine; Others: WAY-181,187
- WAY-208,466
Antagonists: Antidepressants: Amitriptyline
- Amoxapine
- Clomipramine
- Doxepin
- Mianserin
- Nortriptyline; Atypical antipsychotics: Aripiprazole
- Asenapine
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- Ro 63-0563
- SB-258,585
- SB-271,046
- SB-357,134
- SB-399,885
- SB-742,457
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- Agonists: Lysergamides: LSD; Tryptamines: 5-CT
- 5-MT
- Bufotenin; Others: 8-OH-DPAT
- AS-19
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- Sarizotan
Antagonists: Lysergamides: 2-Bromo-LSD
- Bromocriptine
- Dihydroergotamine
- Ergotamine
- Mesulergine
- Metergoline
- Methysergide; Antidepressants: Amitriptyline
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- Agonists: 77-LH-28-1
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- Agonists: 5-HIAA
- A-84,543
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- EVP-4473
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- GTS-21
- Ispronicline
- Lobeline
- MEM-63,908/RG-3487
- Nicotine
- NS-1738
- PHA-543,613
- PHA-709,829
- PNU-120,596
- PNU-282,987
- Pozanicline
- Rivanicline
- RJR-2429
- Sazetidine A
- Sebacylcholine
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- TC-6683
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- UB-165
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- WAY-317,538
- XY-4083
Antagonists: 18-Methoxycoronaridine
- α-Bungarotoxin
- α-Conotoxin
- Alcuronium
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- Tubocurarine
- Vecuronium
- Xenon
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- Cymserine * Many of the acetylcholinesterase inhibitors listed above act as butyrylcholinesterase inhibitors.
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