Iven H, Brasch H, Armah B I
Department of Pharmacology, Medical University, Lübeck, Fed. Rep. of Germany.
Arzneimittelforschung. 1988 Sep;38(9):1298-302.
The positive inotropic agent milrinone and the newly synthesized compound saterinone [+/-)-1,2-dihydro-5-[4-[2-hydroxy-3-[4-(2-methoxyphenyl)-1-piperazinyl] propoxy]phenyl]-6-methyl-2-oxo-3-pyridine-carbonitrile, BDF 8634) dose-dependently increased the contractile force of guinea pig left atria. During a 90-min exposure, 10(-4) mol/l saterinone caused a continuous increase of the functional refractory period (FRP), while the initial positive inotropic effect faded gradually. No change of the FRP was observed with milrinone. Saterinone (10(-4) mol/l) also increased the action potential duration and the FRP of guinea pig papillary muscles, while milrinone had no influence on either parameter. Both milrinone and saterinone increased the amplitude, depolarization velocity and duration of slow response action potentials in K+-depolarized muscles. These effects appeared in the presence of tetrodotoxin or propranolol and could be reversed by carbachol. It is concluded that saterinone increases the force of contraction and the slow inward current by inhibiting cardiac phosphodiesterase. The increase of the FRP may be attributed to a decrease of the membrane K+ conductance.
正性肌力药物米力农和新合成的化合物沙替利农[（±）-1,2-二氢-5-[4-[2-羟基-3-[4-（2-甲氧基苯基）-1-哌嗪基]丙氧基]苯基]-6-甲基-2-氧代-3-吡啶甲腈，BDF 8634]剂量依赖性地增加豚鼠左心房的收缩力。在90分钟的暴露期间，10^-4mol/L的沙替利农使功能性不应期（FRP）持续增加，而最初的正性肌力作用逐渐消退。米力农未观察到FRP的变化。沙替利农（10^-4mol/L）也增加了豚鼠乳头肌的动作电位持续时间和FRP，而米力农对这两个参数均无影响。米力农和沙替利农均增加了钾离子去极化肌肉中慢反应动作电位的幅度、去极化速度和持续时间。这些作用在存在河豚毒素或普萘洛尔的情况下出现，并且可被卡巴胆碱逆转。结论是沙替利农通过抑制心脏磷酸二酯酶增加收缩力和慢内向电流。FRP的增加可能归因于膜钾离子电导的降低。
