Weirich J, Antoni H
Department of Physiology, University of Freiburg i. Br., F.R.G.
J Cardiovasc Pharmacol. 1988 Dec;12(6):664-71. doi: 10.1097/00005344-198812000-00007.
Frequency- and voltage-dependent electrophysiologic effects of a chemically novel compound, nicainoprol, were evaluated by recording transmembrane action potentials (APs) from papillary muscles and electrograms (EGs) from isolated perfused hearts of guinea pigs. At 0.2 Hz stimulation, nicainoprol (3.3 x 10(-6) M and 10(-5) M) significantly reduces the maximal upstroke velocity (Vmax) of APs without significant change in resting membrane potential (RMP), functional refractory period (FRP), and action potential duration. Nicainoprol prolongs the spread of excitation but has little effect on the duration of the ventricular EG. The Vmax depression is frequency dependent in the range of 0.02-2.5 Hz, showing saturation at higher frequencies. Under resting conditions, nicainoprol (3.3 x 10(-6) M and 10(-5) M) has no effect on Vmax. The onset of frequency-dependent Vmax reduction follows monoexponential time courses with rate constants of 0.053 +/- 0.007 AP-1 (3.3 x 10(-6) M) and of 0.066 +/- 0.005 AP-1 (10(-5) M) at 1 Hz. Vmax recovers from frequency-dependent depression with time constants of 45.4 +/- 3.2 s (3.3 x 10(-6) M) and 48.4 +/- 3.5 s (10(-5) M). Nicainoprol significantly shifts the Vmax-RMP relation in hyperpolarizing direction by 2.6 +/- 1.1 mV (3.3 x 10(-6) M) and 5.4 +/- 1.3 mV (10(-5) M) at membrane potentials where Vmax is half maximal. It is concluded that nicainoprol can be classified as a class 1C drug and does preferentially bind to inactivated sodium channels with a dissociation constant of about 10(-5) M.
通过记录豚鼠乳头肌的跨膜动作电位（APs）和离体灌注心脏的心电图（EGs），评估了一种化学结构新颖的化合物尼卡诺普的频率和电压依赖性电生理效应。在0.2 Hz刺激下，尼卡诺普（3.3×10⁻⁶ M和10⁻⁵ M）显著降低动作电位的最大上升速度（Vmax），而静息膜电位（RMP）、功能不应期（FRP）和动作电位持续时间无显著变化。尼卡诺普延长了兴奋的传播，但对心室心电图的持续时间影响很小。Vmax抑制在0.02 - 2.5 Hz范围内呈频率依赖性，在较高频率时表现出饱和。在静息条件下，尼卡诺普（3.3×10⁻⁶ M和10⁻⁵ M）对Vmax无影响。频率依赖性Vmax降低的起始遵循单指数时间进程，在1 Hz时，速率常数分别为0.053±0.007 AP⁻¹（3.3×10⁻⁶ M）和0.066±0.005 AP⁻¹（10⁻⁵ M）。Vmax从频率依赖性抑制中恢复的时间常数分别为45.4±3.2 s（3.3×10⁻⁶ M）和48.4±3.5 s（10⁻⁵ M）。在Vmax为最大值一半的膜电位处，尼卡诺普使Vmax - RMP关系显著向超极化方向偏移2.6±1.1 mV（3.3×10⁻⁶ M）和5.4±1.3 mV（10⁻⁵ M）。结论是，尼卡诺普可归类为1C类药物，并且确实优先与失活的钠通道结合，解离常数约为10⁻⁵ M。
