General pharmacology of IY-81149, a new proton pump inhibitor

IY-81149 (2-[(4-methoxy-3-methyl)-2-pyridinyl]methylsulfinyl]-5-(1H-pyrrol- 1-yl-)-1H-benzinidazole, CAS 172152-36-2) is a new proton pump inhibitor an d expected to be an antiulcer drug. Its general pharmacological effects wer e studied in this paper. The doses given were vehicle control, 0.3, 1, 3, 1 00, 300 and 1000 mg/ kg and were administered orally. The animals used in t his study were mouse, rat, guinea pig and beagle dog. IY-81149 decreased sp ontaneous locomotor activity at 1000 mg/kg and showed a weak effect in moto r performance at 300 and 1000 mg/kg. IY-81149 prolonged the hexobarbital-in duced sleeping time dose dependently at 100, 300 and 1000 mg/kg. Oral admin istration of IY-81149 caused a dose-dependent hypothermic effect up to 300 mg/kg and showed analgesic effect at 1000 mg/kg. IY-81149 produced an anti- secretory effect in pylorus ligated rats. The total gastric volume and acid ity were significantly decreased at doses ranging from 1 to 3 mg/kg. Howeve r, IY-81149 had no effects on general behavior, did not show anticonvulsant activity, and did not affect blood pressure and heart rate, LVP (Left vent ricular peak systolic pressure), LVEDP (left ventricular end diastolic pres sure), LVDP (left ventricular developing pressure), DP (double product), HR (heart rate), CFR (coronary flow rate), smooth muscle contraction, respira tion, intestinal transport and renal function. These findings demonstrate t hat IY-81149 possesses weak central nervous system action and inhibitory ef fects on microsomal enzymes and gastric secretion after single administrati on. The results suggest that IY-81149 does not exert any notable pharmacolo gical effects on the cardiovascular system, autonomic nerve system or smoot h muscle function at all doses tested.