General pharmacological properties of the new proton pump inhibitor (+/-)-5-methoxy-2-[[(4-methoxy-3,5-dimethylpyrid-2-yl)methyl] sulfinyl]-1H-imidazo[4,5-b]pyridine

The general pharmacological profiles of a novel proton pump inhibitor; (+/- )-5-methoxy-2[[(4-methoxy-3,5-dimethylpyrid-2-yl)methyl]sulfinyl]-1H-imidaz o[4,5b]pyridine, TU-199) on the central nervous system, cardiorespiratory s ystem, autonomic nervous system, gastrointestinal system and renal function s 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 admin istration in mice. TU-199 had no effect on pentobarbital-induced hypnosis, analgesic activity and electroshock-induced convulsion in mice, and on rect al temperature in rats. However, TU-199 (300 mg/kg p.o.) showed slight anti convulsant activity on pentylenetetrazole-induced convulsion in mice. TU-19 9 had no effect on respiratory rate, blood pressure, heart rate, femoral bl ood flow and electrocardiogram in anesthetized dogs. TU-199 (10(-4) M) caus ed 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 pic ileum and had no effect on intestinal motility in mice, gastric emptying in rats, bile secretion in ra ts and carbachol-induced salivary secretion in mice. TU-199 had no effect o n urinary volume and excretion of electrolytes in rats. These results sugge st that TU-199 does not induce serious adverse effects on the central nervo us system, cardiorespiratory system, autonomic nervous system, gastrointest inal system and renal functions with the exception of a decrease in spontan eous motor activity with high doses. (C) 1999 Prous Science. All rights res erved.