Dabasaki T, Kobayashi K, Kato Y, Uemura A
Fuji Central Research Laboratories, Mochida Pharmaceutical Co., Ltd., Shizuoka, Japan.
Nihon Yakurigaku Zasshi. 1992 Nov;100(5):433-44. doi: 10.1254/fpj.100.433.
We examined the effects of M6434 on mean blood pressure and heart rate in conscious rabbits and dogs and on experimental models of postural hypotension in conscious rabbits and anesthetized dogs. M6434, given orally, elevated the mean blood pressure in conscious rabbits and dogs. The pressor effect of M6434 was more potent than that of midodrine, but the bradycardiac action of M6434 was weaker than that of midodrine. M6434 (1.0 and 3.0 mg/kg, p.o.) prevented the head-up tilt-induced reductions of mean blood pressure and cerebral tissue blood flow in conscious rabbits, and these effects of M6434 were about 3 times more potent than those of midodrine. In the postural hypotension of anesthetized dogs, M6434 at the doses more than 10 micrograms/kg, i.v. also produced the preventive effects on mean blood pressure and cerebral tissue blood flow. These effects of M6434 were about 10-30 times more potent than those of midodrine. These results show that M6434 possesses a potent hypertensive effect with a weaker bradycardiac action and suggest that M6434 may be a potential candidate for an anti-hypotensive agent that can prevent the deterioration of hemodynamics in postural hypotension.
我们研究了M6434对清醒兔和犬的平均血压及心率的影响，以及对清醒兔和麻醉犬体位性低血压实验模型的影响。口服M6434可升高清醒兔和犬的平均血压。M6434的升压作用比米多君更强，但M6434的心动过缓作用比米多君弱。M6434（1.0和3.0mg/kg，口服）可防止清醒兔因头高位倾斜引起的平均血压和脑组织血流降低，且M6434的这些作用比米多君强约3倍。在麻醉犬的体位性低血压模型中，静脉注射剂量超过10μg/kg的M6434也可对平均血压和脑组织血流产生预防作用。M6434的这些作用比米多君强约10 - 30倍。这些结果表明，M6434具有强效的升压作用且心动过缓作用较弱，提示M6434可能是一种潜在的抗低血压药物候选物，可预防体位性低血压时血流动力学的恶化。
