| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
Purity: ≥98%
| Targets |
5-HT4 receptor (human 5-HT4a and 5-HT4b subtypes with pKi of 8.6 and 8.1, respectively); shows >290-fold selectivity over other 5-HT receptor subtypes.
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| ln Vitro |
Prucalopride induces contractions in a concentration-dependent manner with pEC50 of 7.5. Prucalopride (1 mM) significantly amplifies the rebound contraction of the guinea-pig proximal colon after electrical field stimulation. Prucalopride induces relaxation of the rat oesophagus preparation of rat oesophagus tunica muscularis mucosae with pEC50 of 7.8, yielding a monophasic concentration–response curve.
Kinase Assay: Prucalopride is a novel enterokinetic compound and is the first representative of the benzofuran class. We set out to establish its pharmacological profile in various receptor binding and organ bath experiments. Receptor binding data have demonstrated prucaloprides high affinity to both investigated 5-HT(4) receptor isoforms, with mean pK(i) estimates of 8.60 and 8.10 for the human 5-HT(4a) and 5-HT(4b) receptor, respectively. From the 50 other binding assays investigated in this study only the human D(4) receptor (pK(i) 5.63), the mouse 5-HT(3) receptor (pK(i) 5.41) and the human sigma(1) (pK(i) 5.43) have shown measurable affinity, resulting in at least 290-fold selectivity for the 5-HT(4) receptor. Classical organ bath experiments were done using isolated tissues from the rat, guinea-pig and dog gastrointestinal tract, using various protocols. Prucalopride was a 5-HT(4) receptor agonist in the guinea-pig colon, as it induced contractions (pEC(50)=7.48+/-0.06; insensitive to a 5-HT(2A) or 5-HT(3) receptor antagonist, but inhibited by a 5-HT(4) receptor antagonist) as well as the facilitation of electrical stimulation-induced noncholinergic contractions (blocked by a 5-HT(4) receptor antagonist). Furthermore, it caused relaxation of a rat oesophagus preparation (pEC(50)=7.81+/-0.17), in a 5-HT(4) receptor antagonist sensitive manner. Prucalopride did not cause relevant inhibition of 5-HT(2A), 5-HT(2B), or 5-HT(3), motilin or cholecystokinin (CCK(1)) receptor-mediated contractions, nor nicotinic or muscarinic acetylcholine receptor-mediated contractions, up to 10 microM. It is concluded that prucalopride is a potent, selective and specific 5-HT(4) receptor agonist. As it is intended for treatment of intestinal motility disorders, it is important to note that prucalopride is devoid of anti-cholinergic, anticholinesterase or nonspecific inhibitory activity and does not antagonise 5-HT(2A), 5-HT(2B) and 5-HT(3) receptors or motilin or CCK(1) receptors. Cell Assay: Classical organ bath experiments were done using isolated tissues from the rat, guinea-pig and dog gastrointestinal tract, using various protocols. Prucalopride was a 5-HT(4) receptor agonist in the guinea-pig colon, as it induced contractions (pEC(50)=7.48+/-0.06; insensitive to a 5-HT(2A) or 5-HT(3) receptor antagonist, but inhibited by a 5-HT(4) receptor antagonist) as well as the facilitation of electrical stimulation-induced noncholinergic contractions (blocked by a 5-HT(4) receptor antagonist). Furthermore, it caused relaxation of a rat oesophagus preparation (pEC(50)=7.81+/-0.17), in a 5-HT(4) receptor antagonist sensitive manner. Prucalopride demonstrates high affinity for human 5-HT4 receptors (Ki=2.5-8 nM); it acts as a partial agonist at human and porcine atrial 5-HT4 receptors, stimulating gastrointestinal motility. |
| ln Vivo |
Complete bowel movements per week is 30.9% of those receiving 2 mg of Prucalopride and 28.4% of those receiving 4 mg of Prucalopride, as compared with 12.0% in the placebo group. 47.3% of patients receiving 2 mg of Prucalopride and 46.6% of those receiving 4 mg of Prucalopride has an increase in the number of spontaneous, complete bowel movements of one or more per week, on average, as compared with 25.8% in the placebo group. Prucalopride (2 mg or 4 mg) significantly improves all other secondary efficacy end points, including patients satisfaction with their bowel function and treatment and their perception of the severity of their constipation symptoms. Prucalopride (4 mg daily) accelerates overall gastric emptying and small bowel transit in patients with constipation without a rectal evacuation disorder. Prucalopride (4 mg daily) tends to accelerate overall colonic transit with significantly faster overall colonic transit and ascending colon emptying. Higher proportions of patients on prucalopride 2 mg (19.5%), 4 mg (23.6%) has three or more spontaneous complete bowel movements(SCBM)/week compared with placebo (9.6%). Prucalopride also significantly improves secondary efficacy and quality of life endpoints, including the proportion of patients with an increase of one or more SCBM/week, evacuation completeness, perceived disease severity and treatment effectiveness and quality of life. Prucalopride alters colonic contractile motility patterns in a dose-dependent fashion by stimulating high-amplitude clustered contractions in the proximal colon and by inhibiting contractile activity in the distal colon of fasted dogs. Prucalopride also causes a dose-dependent decrease in the time to the first giant migrating contraction (GMC); at higher doses of prucalopride, the first GMC generally occurres within the first half-hour after treatment.
In vivo, prucalopride stimulates colonic motility and accelerates gastrointestinal transit, producing prokinetic effects and relieving constipation in animal models and humans. |
| Enzyme Assay |
Receptor binding affinity is determined using radioligand displacement assays on membranes from cells expressing human 5-HT4 receptors; functional activity is assessed using cAMP accumulation assays.
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| Cell Assay |
Cells expressing 5-HT4 receptors are treated with prucalopride; receptor-mediated cAMP production, calcium mobilization, or reporter gene expression is measured to assess agonist activity.
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| Animal Protocol |
In vivo efficacy is evaluated in animal models of gastrointestinal motility; colonic transit, gastric emptying, and fecal output are measured following oral administration.
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| References |
Eur J Pharmacol.2001 Jun 29;423(1):71-83;N Engl J Med.2008 May 29;358(22):2344-54.
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| Molecular Formula |
C18H27CL2N3O3
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|---|---|
| Molecular Weight |
403.33
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| Exact Mass |
403.143
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| CAS # |
179474-80-7
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| Related CAS # |
Prucalopride;179474-81-8
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| PubChem CID |
9931054
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
3.983
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
26
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| Complexity |
445
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC1=C(N)C(CCO2)=C2C(C(NC3CCN(CCCOC)CC3)=O)=C1.Cl
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| InChi Key |
KKMOQGWTJRGLNN-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H26ClN3O3.ClH/c1-24-9-2-6-22-7-3-12(4-8-22)21-18(23)14-11-15(19)16(20)13-5-10-25-17(13)14;/h11-12H,2-10,20H2,1H3,(H,21,23);1H
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| Chemical Name |
4-amino-5-chloro-N-[1-(3-methoxypropyl)piperidin-4-yl]-2,3-dihydro-1-benzofuran-7-carboxamide;hydrochloride
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| Synonyms |
R-108512; Prucalopride Succinate; R 108512; R-93877 HCl; R 93877 hydrochloride; R-108512; R108512; Resolor; Resotran; R93877; trade name: Motegrity
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4794 mL | 12.3968 mL | 24.7936 mL | |
| 5 mM | 0.4959 mL | 2.4794 mL | 4.9587 mL | |
| 10 mM | 0.2479 mL | 1.2397 mL | 2.4794 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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