Anti-Hypotensive Effects of M6434, an Orally Active α1-Adrenoceptor Agonist, in Rats

The Japanese Journal of Pharmacology

Tatsuroh Dabasaki¹  Masato Shimojo¹  Akio Uemura¹  Hiroshi Ishikawa¹ 

[1] Fuji Central Research Laboratory, Mochida Pharmaceutical Co., Ltd.

关键词: M6434;    α1-Agonist;    Midodrine;    Postural hypotension;    Orthostatic index;   

DOI  :  10.1254/jjp.59.145

学科分类：药理学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(18)Cited-By(1)The anti-hypotensive effects of M6434 were evaluated and compared with those of other orally active sympathomimetics in rats. Oral administration of M6434 (0.5-2.0 mg/kg) and midodrine (1.0-5.0 mg/kg) also produced a dose-related increase in mean arterial pressure in normotensive rats. The pressor effect of M6434 was about 4 times more potent than that of midodrine. Both M6434 and midodrine caused a dose-dependent decrease in heart rate. The pressor effect of M6434 (1.0 mg/kg) did not diminish after its repeated administration for 7 days. The pretreatment with M6434 (0.5-1.0 mg/kg) and midodrine (2.0-5.0 mg/kg) improved the orthostatic index in the experimental model of postural hypotension in rats. The effect of M6434 on postural hypotension was about 5 times more potent than that of midodrine. Intravenously injected M6434 (3-300 μg/kg) produced a dose-dependent increase in the blood pressure of pithed rats. These results suggest that M6434 possesses a potent anti-hypotensive activity which is superior to that of midodrine, and M6434 may be useful in the treatment of essential and postural hypotension.

【 授权许可】

Unknown