Hirohashi M, Takasuna K, Yamashita N, Tamura K
Research Institute, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
Arzneimittelforschung. 1991 Jan;41(1):9-18.
Respiratory and cardiovascular effects of midaglizole (DG-5128, CAS 66529-17-7) were investigated in comparison with yohimbine, idazoxan and tolbutamide. 1. Respiration: Midaglizole had little or no effect on respiration of anesthetized dogs. Yohimbine and idazoxan augmented respiration at low dose. Tolbutamide depressed respiratory rate and depth at high dose. 2. Blood pressure and heart rate: Midaglizole produced dose-related hypotension and bradycardia in anesthetized dogs which had laparotomy, whereas it had little or no effect on blood pressure and heart rate of dogs which had no laparotomy (unlaparotomized dogs). Tendency of slight hypertension was observed after high dose of tolbutamide in laparotomized dogs, and transient hypotension was induced in unlaparotomized dogs. Yohimbine and idazoxan increased blood pressure at low dose in unlaparotomized dogs. In laparotomized dogs, yohimbine produced hypertension and hypotension at low and high doses, respectively. In isolated guinea pig atria, midaglizole produced bradycardia which was not observed after yohimbine. Tolbutamide decreased the pulse rate at high concentration. 3. Cardiac contractility: Midaglizole produced increase in cardiac contractility of anesthetized dogs. Yohimbine and idazoxan, at low dose, showed similar inotropic activity. Prazosin also produced a positive inotropic effect, whereas tolbutamide lacked the activity. The inotropic effects of midaglizole and yohimbine were antagonized by pretreatment with propranolol or hexamethonium, whereas a similar effect of prazosin was not influenced by both blockers. In isolated guinea pig atria, midaglizole showed slight inotropic activity. Yohimbine was without any effect, whereas tolbutamide reduced the contractile force. 4. Femoral blood flow: Midaglizole produced a transient increase in femoral blood flow and a decrease in femoral arterial resistance of anesthetized dogs. Yohimbine and idazoxan, at low dose, showed similar vasodilator activity. Prazosin also produced a vasodilator effect, whereas tolbutamide lacked the activity. The vasodilator effects of midaglizole and yohimbine were not affected with propranolol, but inhibited after hexamethonium. 5. Mesenteric blood flow: Midaglizole significantly decreased mesenteric blood flow and increased the arterial resistance of anesthetized dogs in a dose dependent manner. Tolbutamide induced a decrease in blood flow and an increase in arterial resistance only at the highest dose used. Yohimbine increased mesenteric blood flow at low dose and decreased it at high dose. 6. Renal blood flow: Midaglizole dose-relatedly decreased renal blood flow of anesthetized dogs. Tolbutamide and yohimbine at high dose produced a long-lasting decrease of the blood flow. Midaglizole produced a slight transient reduction of renal arterial resistance which was followed by a slight increase. Tolbutamide increased the arterial resistance at high dose.(ABSTRACT TRUNCATED AT 400 WORDS)
比较了咪达格列唑（DG - 5128，CAS 66529 - 17 - 7）与育亨宾、咪唑克生和甲苯磺丁脲对呼吸和心血管系统的影响。1. 呼吸：咪达格列唑对麻醉犬的呼吸几乎没有影响。育亨宾和咪唑克生在低剂量时可增强呼吸。甲苯磺丁脲在高剂量时会降低呼吸频率和深度。2. 血压和心率：咪达格列唑在接受剖腹手术的麻醉犬中产生剂量相关的低血压和心动过缓，而对未接受剖腹手术的犬（未剖腹犬）的血压和心率几乎没有影响。在剖腹犬中，高剂量甲苯磺丁脲后观察到轻微高血压倾向，而在未剖腹犬中诱导出短暂低血压。育亨宾和咪唑克生在未剖腹犬的低剂量时会升高血压。在剖腹犬中，育亨宾在低剂量和高剂量时分别产生高血压和低血压。在离体豚鼠心房中，咪达格列唑产生心动过缓，育亨宾则未观察到这种情况。甲苯磺丁脲在高浓度时会降低脉搏率。3. 心肌收缩力：咪达格列唑使麻醉犬的心肌收缩力增强。育亨宾和咪唑克生在低剂量时表现出类似的正性肌力活性。哌唑嗪也产生正性肌力作用，而甲苯磺丁脲缺乏这种活性。咪达格列唑和育亨宾的正性肌力作用可被普萘洛尔或六甲铵预处理拮抗，而哌唑嗪的类似作用不受这两种阻滞剂影响。在离体豚鼠心房中，咪达格列唑表现出轻微的正性肌力活性。育亨宾无任何作用，而甲苯磺丁脲降低收缩力。4. 股动脉血流量：咪达格列唑使麻醉犬的股动脉血流量短暂增加，股动脉阻力降低。育亨宾和咪唑克生在低剂量时表现出类似的血管舒张活性。哌唑嗪也产生血管舒张作用，而甲苯磺丁脲缺乏这种活性。咪达格列唑和育亨宾的血管舒张作用不受普萘洛尔影响，但六甲铵后被抑制。5. 肠系膜血流量：咪达格列唑显著降低麻醉犬的肠系膜血流量，并以剂量依赖方式增加动脉阻力。甲苯磺丁脲仅在使用的最高剂量时诱导血流量减少和动脉阻力增加。育亨宾在低剂量时增加肠系膜血流量，在高剂量时减少。6. 肾血流量：咪达格列唑与剂量相关地降低麻醉犬的肾血流量。甲苯磺丁脲和育亨宾在高剂量时使血流量长期减少。咪达格列唑使肾动脉阻力轻微短暂降低，随后轻微增加。甲苯磺丁脲在高剂量时增加动脉阻力。（摘要截断于400字）
