Nakayama N, Ikezono K, Mori T, Yamashita S, Nakayama S, Tanaka Y, Hosokawa T, Minami Y, Masutani K, Yamamura Y
Second Tokushima Institute of New Drug Research, Otsuka Pharmaceutical Co., Ltd., Japan.
J Cardiovasc Pharmacol. 1990 May;15(5):836-44. doi: 10.1097/00005344-199005000-00021.
The antihypertensive action of OPC-13340, a new dihydropyridine, was studied in rats and compared with the action of nicardipine and other dihydropyridines. OPC-13340 showed more potent and longer hypotensive action than nicardipine when administered either intravenously (i.v.) or orally in normotensive and hypertensive rats. Among 6 compounds tested, (OPC-13340, nifedipine, nitrendipine, nisoldipine, nicardipine and diltiazem), OPC-13340 was the most potent and long-acting when administered orally to spontaneously hypertensive rats (SHR). Tachycardia after administration of OPC-13340 was less or diminished earlier than that of nicardipine. Oral administration of OPC-13340 (3 mg/kg) once daily for 13 days did not cause any rebound phenomena in SHR. The compound inhibited Ca- or K-induced contractions in isolated rat aorta and shortened action potential duration in guinea pig papillary muscle, suggesting Ca channel blocking action. OPC-13340 might be useful as a drug for once-daily therapy of essential hypertension.
研究了新型二氢吡啶OPC - 13340对大鼠的降压作用，并与尼卡地平和其他二氢吡啶的作用进行了比较。在正常血压和高血压大鼠中，静脉注射（i.v.）或口服OPC - 13340时，其降压作用比尼卡地平更强且持续时间更长。在测试的6种化合物（OPC - 13340、硝苯地平、尼群地平、尼索地平、尼卡地平和地尔硫䓬）中，对自发性高血压大鼠（SHR）口服给药时，OPC - 13340的作用最强且持续时间最长。给予OPC - 13340后出现的心动过速比尼卡地平更少或更早减轻。在SHR中，每天口服一次OPC - 13340（3 mg/kg），连续13天，未引起任何反跳现象。该化合物抑制离体大鼠主动脉中钙或钾诱导的收缩，并缩短豚鼠乳头肌的动作电位持续时间，提示其具有钙通道阻滞作用。OPC - 13340可能作为一种用于原发性高血压每日一次治疗的药物。
