title: General pharmacological properties of the new proton pump inhibitor (+/-)-5-methoxy-2-[[(4-methoxy-3,5-dimethylpyrid-2-yl)methyl]sulf inyl]- 1H-imidazo[4,5-b]pyridine.
abstract: The general pharmacological profiles of a novel proton pump inhibitor, (+/-)-5-methoxy-2-[[(4-methoxy-3,5-dimethylpyrid-2-yl)methyl]sulfi nyl]- 1H-imidazo[4,5-b]pyridine, TU-199) on the central nervous system, cardiorespiratory system, autonomic nervous system, gastrointestinal system and renal functions were investigated. TU-199 had no effects on general signs and behavior in mice. TU-199 (300 mg/kg p.o.) decreased locomotor activity 3 h after administration in mice. TU-199 had no effect on pentobarbital-induced hypnosis, analgesic activity and electroshock-induced convulsion in mice, and on rectal temperature in rats. However, TU-199 (300 mg/kg p.o.) showed slight anticonvulsant activity on pentylenetetrazole-induced convulsion in mice. TU-199 had no effect on respiratory rate, blood pressure, heart rate, femoral blood flow and electrocardiogram in anesthetized dogs. TU-199 (10(4) M) caused the cumulative concentration-response curve obtained with acetylcholine in isolated guinea pig ileum to shift to the right. However, TU-199 showed no effect on contraction of isolated guinea pig ileum and had no effect on intestinal motility in mice, gastric emptying in rats, bile secretion in rats and carbachol-induced salivary secretion in mice. TU-199 had no effect on urinary volume and excretion of electrolytes in rats. These results suggest that TU-199 does not induce serious adverse effects on the central nervous system, cardiorespiratory system, autonomic nervous system, gastrointestinal system and renal functions with the exception of a decrease in spontaneous motor activity with high doses.
authors.affiliation: Medicinal Research Group II, Kazusa Research Laboratories, Tokyo Tanabe Co., Ltd., Japan.
authors.forename: B
authors.initials: B
authors.lastname: Kakinoki
authors.forename: C
authors.initials: C
authors.lastname: Ono
authors.forename: N
authors.initials: N
authors.lastname: Yamazaki
authors.forename: N
authors.initials: N
authors.lastname: Chikamatsu
authors.forename: D
authors.initials: D
authors.lastname: Wakatsuki
authors.forename: K
authors.initials: K
authors.lastname: Uchiyama
authors.forename: Y
authors.initials: Y
authors.lastname: Morinaka
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D004285:Dogs; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D009853:Omeprazole / Q000031:analogs & derivatives; D054328:Proton Pump Inhibitors; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D012640:Seizures / Q000517:prevention & control*
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D007093:Imidazoles; D054328:Proton Pump Inhibitors; D011725:Pyridines; D009853:Omeprazole; C119998:Tenatoprazole