Minesapride (hydrobromide)

Minesapride hydrobromide (DSP-6952 hydrobromide) is an orally active, selective 5-HT4 receptor partial agonist. Minesapride hydrobromide enhances gastrointestinal motility, colonic transit and defecation function, and inhibits visceral hypersensitivity. Minesapride hydrobromide 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 hydrobromide can be used in research related to constipation-predominant irritable bowel syndrome, chronic constipation, atonic constipation, spastic constipation, functional constipation and functional dyspepsia^[1][2][3][4]. In Vitro:Minesapride hydrobromide exhibits no inhibitory or inductive activity against cytochrome P450 isozymes in in vitro assays^[1].
Minesapride hydrobromide shows no significant binding affinity for the hERG cardiac potassium channel in in vitro experiments^[1].
Minesapride hydrobromide shows no significant binding affinity for 5-HT₁B, 5-HT₁D or 5-HT₂A receptors in in vitro assays^[1].
Minesapride hydrobromide 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 K_i range of 51.9-95.3 nM^[2].
Minesapride hydrobromide binds tightly to 5-HT₄ (a), 5-HT₄ (b), and 5-HT₄ (c) receptors (with K_i values of 66.9, 51.9, and 95.3 nM, respectively) as well as guinea pig striatal 5-HT₄ receptors (K_i = 63.1 nM)^[4].
Minesapride hydrobromide 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) hydrobromide inhibits hERG currents in hERG-transfected CHO-K1 cells, with an IC₅₀ of 65.4 μM^[4]. In Vivo:Minesapride (0.1-3 mg/kg; i.g.) hydrobromide dose-dependently enhances gastric motility and induces colonic GMCs and defecation in conscious dogs, with ED₅₀ values of 1.56 mg/kg for GMC induction and 2.87 mg/kg for defecation induction^[2].
Minesapride (0.3-10 mg/kg; i.g.) hydrobromide 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.) hydrobromide 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.) hydrobromide 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) hydrobromide 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].