EFFECTS OF ZENECA ZD7288 IN COMPARISON WITH ALINIDINE AND UL-FS-49 ON GUINEA-PIG SINOATRIAL NODE AND VENTRICULAR ACTION-POTENTIALS
EFFECTS OF ZENECA ZD7288 IN COMPARISON WITH ALINIDINE AND UL-FS-49 ON GUINEA-PIG SINOATRIAL NODE AND VENTRICULAR ACTION-POTENTIALS
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DOI：
10.1097/00005344-199409000-00005
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发表时间：
1994-09-01
影响因子：
3
通讯作者：
HEAPY, CG
中科院分区：
文献类型：
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作者：
BRIGGS, I;BOSMITH, RE;HEAPY, CG
ZENECA ZD7288 （4-（n -乙基- n -苯基氨基）- 1,2 -二甲基-6-（甲氨基）嘧啶氯）是一种新型化合物，我们使用传统的微电极技术在豚鼠窦房结（SAN）和乳头肌制剂中与alinidine和UL-FS 49 （zatebradine）进行了比较。在低浓度(1 × 10（-8)-1 × 10(-6)M）下，ZD7288导致SAN起搏器细胞舒张期去极化速率减慢，从而延长舒张期间期，减慢心跳速率。Alinidine和UL-FS 49对舒张去极化率也有类似的影响，但ZD7288在具有“选择性心动过缓”作用的浓度下对SAN细胞的动作电位持续时间（APD）的延长最小。“ZD7288仅在相对高浓度(3 × 10（-6)M-1 × 10(-4)M）时影响豚鼠乳头肌心室细胞的APs，这缩短了平台电位持续时间，尽管总APD受到的影响较小。在这些高浓度下还观察到收缩力（FOC）的降低；只有当浓度大于或等于3 × 10(-5)M时，才会对AP V-max产生显著影响。Alinidine对乳头肌也有负性肌力作用，但其作用浓度与心动过缓作用相似；相反，UL-FS 49具有明显的正性肌力作用，并在心动过缓的浓度范围内增加心室APD。这些数据为ZD7288对心率（HR）的选择性作用提供了依据。
ZENECA ZD7288 (4-(N-ethyl-N-phenylamino)-1 ,2-dimethyl-6-(methylamino) pyrimidinium chloride) is a novel compound which we compared with alinidine and UL-FS 49 (zatebradine) in guinea pig sinoatrial node (SAN) and papillary muscle preparations, using conventional microelectrode techniques. At low concentrations (1 x 10(-8)-1 x 10(-6)M), ZD7288 caused slowing of the diastolic depolarisation rate of SAN pacemaker cells, thus prolonging the diastolic interval and slowing the beating rate. Alinidine and UL-FS 49 also had qualitatively similar effects on diastolic depolarisation rate, but ZD7288 caused least prolongation of the action potential duration (APD) of SAN cells at the concentrations that had ''selective bradycardic actions.'' ZD7288 affected the APs of ventricular cells in guinea pig papillary muscle only at relatively high concentrations (3 x 10(-6)M-1 x 10(-4)M), which reduced plateau potential duration, although total APD was less affected. Reduced force of contraction (FOC) was also observed at these high concentrations; significant effects on AP V-max were noted only at concentrations greater than or equal to 3 x 10(-5)M. Alinidine also had negative inotropic effects on papillary muscle, but its effects were noted at concentrations similar to those with bradycardic actions; in contrast, UL-FS 49 had marked positive inotropic actions and also increased ventricular APD within the bradycardic concentration range. These data provide a basis for the selective actions of ZD7288 on heart rate (HR).