Minesapride
Minesapride (DSP-6952 free base) is an orally active, selective 5-HT4 receptor partial agonist. Minesapride enhances gastrointestinal motility, colonic transit and defecation function, and inhibits visceral hypersensitivity. Minesapride does not inhibit/induce cytochrome P450 isozymes, has no significant affinity for hERG, and does not trigger the risk of cardiac ischemia via coronary vasoconstriction. Minesapride can be used in research related to constipation-predominant irritable bowel syndrome, chronic constipation, atonic constipation, spastic constipation, functional constipation and functional dyspepsia.
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- CAS No.: 1184662-54-1
- 화학식: C21H31ClN4O5
- 분자량:454.95
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보관:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
- 순도&문서
- References
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Help & FAQs
All 5-HT Receptor Isoforms
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Biological Activity
제품 설명
IC50 & Target
[1]|
5-HT4 Receptor |
In Vitro
Minesapride exhibits no inhibitory or inductive activity against cytochrome P450 isozymes in in vitro assays[1].
Minesapride shows no significant binding affinity for the hERG cardiac potassium channel in in vitro experiments[1].
Minesapride shows no significant binding affinity for 5-HT1B, 5-HT1D or 5-HT2A receptors in in vitro assays[1].
Minesapride binds to cell membranes of CHO cells stably transfected with human 5-HT4 (a), 5-HT4 (b), and 5-HT4 (c) receptors, as well as to cell membranes of guinea pig striatal tissues, with a Ki range of 51.9-95.3 nM[2].
Minesapride binds tightly to 5-HT4 (a), 5-HT4 (b), and 5-HT4 (c) receptors (with Ki values of 66.9, 51.9, and 95.3 nM, respectively) as well as guinea pig striatal 5-HT4 receptors (Ki = 63.1 nM)[4].
Minesapride induces concentration-dependent contractions in distal colonic LMMP preparations of guinea pigs, with an EC50 of 271.6 nM and an intrinsic activity of 57% relative to 5-HT[4].
Minesapride (10-100 μM) inhibits hERG currents in hERG-transfected CHO-K1 cells, with an IC50 of 65.4 μM[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
Minesapride (0.3-10 mg/kg; i.g.) dose-dependently enhances colonic transit rate in guinea pigs via activation of 5-HT4 receptors, with significant effects seen at doses of 3 mg/kg and 10 mg/kg[2].
Minesapride (0.3-10 mg/kg; p.o.) dose-dependently increases fecal wet weight in mice without altering fecal fluid content, indicating enhanced defecation without diarrhea[2].
Minesapride (0.03-3 mg/kg; p.o.) dose-dependently improves Clonidine (HY-12721)-induced atonic constipation in mice, with an ED50 of 0.429 mg/kg[2].
DSP-6952 (6-180 mg/kg; p.o.; single dose) does not affect ECG parameters or blood pressure up to 180 mg/kg p.o. in conscious cynomolgus monkeys, but causes a transient, dose-dependent increase in heart rate that is significant at 180 mg/kg p.o[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Nosan-Beagle (male; surgically implanted force transducers on gastric antrum and colon, plus intragastric administration tube)[2]
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Dosage:0.1 mg/kg; 0.3 mg/kg; 1 mg/kg; 3 mg/kg
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Administration:i.g.
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Result:Enhanced gastric motility in a dose-dependent manner, with gastric motor index values of 117.5%, 138.6%, 126.4%, and 140.7% for the 0.1, 0.3, 1, and 3 mg/kg doses, respectively.
Induced colonic GMCs in 0/10, 1/10, 4/10, and 6/9 dogs at the 0.1, 0.3, 1, and 3 mg/kg doses, respectively, with an ED50 of 1.56 mg/kg for GMC induction.
Induced defecation in 0/10, 0/10, 3/10, and 4/9 dogs at the 0.1, 0.3, 1, and 3 mg/kg doses, respectively, with an ED50 of 2.87 mg/kg for defecation induction.
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Animal Model:Slc: Hartley (male; surgically implanted intragastric and colonic administration tubes)[2]
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Dosage:0.3 mg/kg; 1 mg/kg; 3 mg/kg; 10 mg/kg
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Administration:i.g.
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Result:Enhanced colonic transit rate in a dose-dependent manner, with significant increases at 3 mg/kg and 10 mg/kg.
Had its enhancement of colonic transit rate antagonized by the 5-HT4 receptor antagonist SB-207266.
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Animal Model:Slc: ddY (male)[2]
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Dosage:0.3 mg/kg; 1 mg/kg; 3 mg/kg; 10 mg/kg
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Administration:p.o.
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Result:Increased cumulative fecal wet weight over 0-120 minutes in a dose-dependent manner, with significant increases at 1 mg/kg, 3 mg/kg, and 10 mg/kg.
Did not increase fecal fluid content at any dose tested, with fluid content remaining near baseline levels of ~52-56%.
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Animal Model:Macaca fascicularis (male, 3-4 years old, 3.3-3.9 kg)[4]
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Dosage:6 mg/kg; 20 mg/kg; 60 mg/kg; 180 mg/kg
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Administration:p.o.; single dose
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Result:Showed no statistically significant changes in PQ interval, QRS duration, QTc, or blood pressure at doses up to 180 mg/kg.
Caused a transient, dose-dependent increase in heart rate starting at 20 mg/kg (1 hour post-administration), with a significant increase at 180 mg/kg; all parameters returned to normal ranges by 3-7 hours post-administration.
Reached mean maximum plasma concentrations (Cmax) of 723 ng/mL (6 mg/kg), 4840 ng/mL (20 mg/kg), 19100 ng/mL (60 mg/kg), and 98100 ng/mL (180 mg/kg).
Showed no abnormal general behavior.
Chemical Information
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CAS No. 1184662-54-1
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분자량 454.95
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화학식 C21H31ClN4O5
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SMILES
OCC(N(CC1)CCC1CN(CCO2)C[C@@H]2CNC(C3=C(C=C(C(Cl)=C3)N)OC)=O)=O
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Synonyms
DSP-6952 free base
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선적
Room temperature in continental US; may vary elsewhere.
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보관
Please store the product under the recommended conditions in the Certificate of Analysis.
순도&문서
References
[1]. Fukudo S, et al. Efficacy and Safety of 5-HT4 Receptor Agonist Minesapride for Irritable Bowel Syndrome with Constipation in a Randomized Controlled Trial. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2021 Mar;19(3):538-546.e8. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Minesapride Related Classifications
HY-109065 Related Classifications
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