Kido H, Nishikawa M, Hayashi K, Kubo Y, Ebisu H, Egi Y, Shinyama H, Nakamura N
Central Research Laboratories, Green Cross Corporation, Osaka, Japan.
Nihon Yakurigaku Zasshi. 1997 Jun;109(6):291-301. doi: 10.1254/fpj.109.291.
The antihypertensive effects of AE0047, a novel 1,4-dihydropyridine-type calcium antagonist, were investigated in spontaneously hypertensive rats (SHR/crj) and two kidney-one clip renal hypertensive dogs (RHD). AE0047, which was orally administered at the dose of 0.3, 1 or 3 mg/kg once daily for 8 consecutive weeks to SHR/crj, exhibited a dose-related decrease in systolic blood pressure. The antihypertensive action was reinforced during the drug treatment at 0.3 and 1 mg/kg. At each dose, the trough-to-peak (T/P) ratio was above 0.50 two weeks later. Although the reflex tachycardia was observed at 1 or 3 mg/kg on the 1st day, it gradually weakened within 8 weeks. Long-term treatment with AE0047 led to the regression of left ventricular hypertrophy. Furthermore, AE0047 had no influences on lipid and glucose metabolism. In RHD, and AE0047 capsule (GJ-0956) containing 2 or 8 mg of the drug was administered for 2 weeks. GJ-0956 produced no reduction in blood pressure at 2 mg, but enhanced the antihypertensive effect starting at 8 mg. The T/P ratios were 0.52 and 0.67 for the systolic and diastolic pressure, respectively, on the 14th day. These results indicate that AE0047 may be expected to exhibit beneficial effects for the clinical treatment of hypertension.
研究了新型1,4 - 二氢吡啶类钙拮抗剂AE0047对自发性高血压大鼠（SHR/crj）和二肾一夹肾性高血压犬（RHD）的降压作用。连续8周每天一次给SHR/crj口服剂量为0.3、1或3 mg/kg的AE0047，收缩压呈现剂量相关的下降。在0.3和1 mg/kg药物治疗期间，降压作用增强。在各剂量下，两周后的谷峰（T/P）比值均高于0.50。虽然在第1天1或3 mg/kg剂量时观察到反射性心动过速，但在8周内逐渐减弱。AE0047长期治疗导致左心室肥厚消退。此外，AE0047对脂质和葡萄糖代谢无影响。在RHD中，给予含2或8 mg药物的AE0047胶囊（GJ - 0956）2周。2 mg的GJ - 0956未降低血压，但从8 mg开始增强了降压作用。在第14天，收缩压和舒张压的T/P比值分别为0.52和0.67。这些结果表明，AE0047有望对高血压的临床治疗产生有益作用。
