Mizagliflozin, a novel selective SGLT1 inhibitor, exhibits potential in the amelioration of chronic constipation.

Chronic constipation is a highly common functional gastrointestinal disorder that adversely affects patient quality of life. At present, limited therapeutic options are available for the treatment of chronic constipation, which indicates the need for new therapeutic agents. Herein, we report the potential of mizagliflozin, a novel selective sodium glucose co-transporter 1 (SGLT1) inhibitor, for the amelioration of chronic constipation.

Salivation triggered by pilocarpine involves aquaporin-5 in normal rats but not in irradiated rats.

1. Using rats, we examined the muscarinic receptor subtype mediating pilocarpine-induced parotid salivary secretion and the contributions of ion transporter systems (effluxes of K+ and Cl(-)) and aquaporin-5 (AQP5) translocation to this response in parotid glands in irradiated-induced xerostomia. 2.

Effects of pilocarpine hydrochloride and cevimeline on submandibular/sublingual salivation in rat xerostomia model produced by X-ray irradiation.

The present study was performed to assess the effects of pilocarpine hydrochloride ((3S,4R)-3-ethyl-dihydro-4-[(1-methyl-1H-imidazole-5-yl)methyl]-2(3H)-furanone monohydrochloride, CAS 54-71-7) and cevimeline ((+/-)-cis-2-methylspiro[1,3-oxathiolane-5,3'-quinuclidine] hydrochloride, hemihydrate, CAS 153504-70-2), muscarinic receptor agonists, on salivary secretion from the submandibular/sublingual (SM/SL) glands in normal rats and in rats with xerostomia induced by X-ray (15 Gy) irradiation. To clarify their pharmacological safety profiles, the two drugs were further compared with regard to subtype selectivity for muscarinic receptors (M1, M2, and M3) and central nervous, respiratory, and cardiovascular effects. Pilocarpine hydrochloride (0.

Secretion of saliva in X-irradiated rat submandibular glands.

The mechanism of radiation-induced dysfunction in rat submandibular glands was investigated at the cellular level. After X irradiation (single dose, 15 Gy), a vacuolation in the acinar cells or an enlargement of the acinar lumen was observed as a typical morphological change for 2 weeks. As observed using a video-enhanced contrast differential interference contrast (VEC-DIC) microscope, exocytosis and shrinkage of the acinar cells induced by application of pilocarpine (100 microM) were markedly suppressed for 5 days and then recovered to 80% of the control levels.