Kammer T, Berger F, Borchard U, Hafner D
Institute of Pharmacology, University of Düsseldorf Fed. Rep. of Germany.
Arzneimittelforschung. 1993 Mar;43(3):302-8.
In isolated guinea-pig papillary muscle ([K+]o: 4.7 mmol/l, stimulation rate: 1 Hz) the verapamil derivative NN-bis-(3,4-dimethoxyphenethyl)-N-methylamine)-HCl (YS035; 0.3-100 mumol/l) increased the action potential duration measured at 90% repolarization level (APD90) up to 132% of control and enhanced the force of contraction (Fc) up to 125% of control while resting potential (RP) and the maximum upstroke velocity (Vmax) remained nearly unchanged. At 300 mumol/l YS 035, the membrane became depolarised and action potentials could no longer be elicited. These effects were reversed during wash-out. The increase of ADP90 was largest at 0.05 Hz, and the drug-induced effect continuously declined with an increase in stimulation frequency to 2 Hz. Control ADP90 was correlated to the absolute increase of ADP90 (r = 0.84). In atrial muscle the effect of YS 035 on APD90 was more pronounced than in papillary muscle. The Vmax of slow responses ([K+]o: 27 mmol/l, [Ba2+]o: 0.5 mmol/l) was not affected by concentrations as high as 30 mumol/l YS 035, whereas APD90 was enhanced. An increase in the stimulation rate (0.05 to 0.33 Hz) induced only a small decrease of Vmax at 100 mumol/l YS 035. According to this electrophysiological characterisation YS 035 shows Class III antiarrhythmic properties.
在分离的豚鼠乳头肌中（细胞外钾离子浓度[K⁺]o：4.7 mmol/L，刺激频率：1 Hz），维拉帕米衍生物NN-双-(3,4-二甲氧基苯乙基)-N-甲胺盐酸盐（YS035；0.3 - 100 μmol/L）使在复极化90%水平测量的动作电位时程（APD90）增加至对照的132%，并使收缩力（Fc）增强至对照的125%，而静息电位（RP）和最大除极速度（Vmax）几乎保持不变。在300 μmol/L YS035时，膜发生去极化，不再能诱发动作电位。这些效应在洗脱过程中逆转。APD90的增加在0.05 Hz时最大，药物诱导的效应随着刺激频率增加至2 Hz而持续下降。对照APD90与APD90的绝对增加相关（r = 0.84）。在心房肌中，YS035对APD90的作用比在乳头肌中更明显。慢反应的Vmax（细胞外钾离子浓度[K⁺]o：27 mmol/L，细胞外钡离子浓度[Ba²⁺]o：0.5 mmol/L）不受高达30 μmol/L YS035浓度的影响，而APD90增强。刺激频率增加（从0.05至0.33 Hz）在100 μmol/L YS035时仅引起Vmax的小幅下降。根据这种电生理特性，YS035显示出Ⅲ类抗心律失常特性。
