Wolf P S, Mann W S, Suh J T, Loev B, Smith R D
Fed Proc. 1984 Apr;43(5):1322-5.
Pivalopril (RHC 3659-(S); (S)-N-cyclopentyl-N-(2-methyl-3-pivaloylthiopropionyl) glycine) is a new compound with a hindered sulfur group that has been compared to captopril for oral angiotensin-converting enzyme (ACE) inhibition in rats and dogs and antihypertensive activity in rats. In separate groups of conscious normotensive rats, pivalopril (0.03-1.0 mg/kg, orally [p.o.]) produced a dose-related antagonism of angiotensin I (AngI)-induced pressor effects. The ED50 for pivalopril and captopril was 0.1 mg/kg. In conscious normotensive dogs, pivalopril (incremental doses of 0.01-1.0 mg/kg, p.o.) produced a dose-related antagonism of AngI pressor effects. The ED50 was 0.17 mg/kg for pivalopril and 0.06 mg/kg for captopril. At equieffective doses the two compounds had similar durations of action. In sodium-deficient, conscious spontaneously hypertensive rats (SHR), pivalopril (1-100 mg/kg, p.o.) produced a dose-related reduction in mean arterial pressure. The potency and duration were similar to those of captopril. In the sodium-replete SHR, 5 days of oral dosing with pivalopril, 100 mg/(kg . day), decreased mean arterial pressure more effectively than captopril, 100 mg/(kg . day). No tolerance developed to the antihypertensive effect of either drug. It is concluded that pivalopril is a potent, orally effective ACE inhibitor and antihypertensive agent.
匹伐普利（RHC 3659-(S)；(S)-N-环戊基-N-(2-甲基-3-新戊酰硫代丙酰基)甘氨酸）是一种新型化合物，其含有的受阻硫基团已在大鼠和犬中与卡托普利进行了比较，用于口服血管紧张素转换酶（ACE）抑制作用以及在大鼠中的降压活性。在清醒的正常血压大鼠的不同组中，匹伐普利（0.03 - 1.0毫克/千克，口服[p.o.]）对血管紧张素I（AngI）诱导的升压作用产生剂量相关的拮抗作用。匹伐普利和卡托普利的半数有效剂量（ED50）均为0.1毫克/千克。在清醒的正常血压犬中，匹伐普利（递增剂量0.01 - 1.0毫克/千克，口服）对AngI升压作用产生剂量相关的拮抗作用。匹伐普利的ED50为0.17毫克/千克，卡托普利为0.06毫克/千克。在等效剂量下，这两种化合物具有相似的作用持续时间。在缺钠的清醒自发性高血压大鼠（SHR）中，匹伐普利（1 - 100毫克/千克，口服）使平均动脉压产生剂量相关的降低。其效力和持续时间与卡托普利相似。在钠充足的SHR中，口服匹伐普利100毫克/（千克·天），连续5天，比口服卡托普利100毫克/（千克·天）更有效地降低平均动脉压。两种药物的降压作用均未产生耐受性。结论是匹伐普利是一种强效的口服有效的ACE抑制剂和降压药。
