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.