Gerster P, Riegger C, Fallert M
Arzneimittelforschung. 1987 Mar;37(3):309-15.
4-(2-Difluoromethoxyphenyl)-2-methyl-5-oxo-1,4,5,7-tetrahydro- furo[3,4-b]pyridine-3-carboxylic acid ether ester (CGP 28 392), a dihydropyridine derivative with an annellated lactone ring, was examined in automatically discharging calf Purkinje fibres. Velocity of spontaneous depolarization during both the early and the late phase of the diastolic pause and the rate of rise of the action potential were increased, with the threshold potential at which the upstroke is generated being unaltered. These findings are discussed in terms of ionic mechanisms, including in particular the contribution of sodium ions during the late phase of the diastolic depolarization and the novel type of calcium channel which is supposed to contribute to pacemaker depolarization and action potential initiation. In general, the effects of equimolar concentrations of nifedipine were opposite to those of CGP 28 392. At 1 X 10(-5) mol/l, however, both CGP 28 392 and nifedipine accelerated the late phase of diastolic depolarization. In electrically stimulated, partially depolarized guinea-pig papillary muscles, CGP 28 392 also prolonged the slow action potential and markedly increased inotropism. In equimolar concentrations nifedipine shortened the slow action potential and inhibited contractility. The effects of CGP 28 392 are thus compatible with facilitation of calcium entry and--in Purkinje fibres--also with enhancement of fast sodium conductivity.
4-(2-二氟甲氧基苯基)-2-甲基-5-氧代-1,4,5,7-四氢呋喃并[3,4-b]吡啶-3-羧酸乙酯（CGP 28 392）是一种带有稠合内酯环的二氢吡啶衍生物，在自动放电的小牛浦肯野纤维中进行了研究。舒张期停顿的早期和晚期自发去极化速度以及动作电位的上升速率均增加，而产生上升支的阈电位未改变。从离子机制方面对这些发现进行了讨论，特别包括舒张期去极化后期钠离子的作用以及被认为有助于起搏器去极化和动作电位起始的新型钙通道。一般来说，等摩尔浓度的硝苯地平的作用与CGP 28 392的作用相反。然而，在1×10⁻⁵mol/L时，CGP 28 392和硝苯地平都加速了舒张期去极化的后期。在电刺激的部分去极化豚鼠乳头肌中，CGP 28 392也延长了慢动作电位并显著增加了心肌收缩力。在等摩尔浓度下，硝苯地平缩短了慢动作电位并抑制了收缩性。因此，CGP 28 392的作用与促进钙内流以及在浦肯野纤维中增加快速钠电导相一致。
