Frechilla D, Castiella E, Lasheras B, Cenarruzabeitia E, Monge A, Aldana I, Alvarez T, Losa M J, Font M
Pharmacology Department, Universidad de Navarra, Pamplona, Spain.
J Cardiovasc Pharmacol. 1993 Jan;21(1):89-94. doi: 10.1097/00005344-199301000-00013.
DF-100, i.e., 1-hydrazino-4-(3,5-dimethyl-1-pyrazolyl)-5H-pyridazino[4,5-b ]indole is a new pyridazino[4,5-b]indole derivative related to dihydralazine. The inhibitory effects of DF-100 were investigated on the contractions in isolated aorta and portal vein. In rat aorta, DF-100 inhibited both K(+)-induced as well as norepinephrine-induced contractions. DF-100 also caused dose-dependent relaxation of contractions produced by 80 mM K+. Moreover, DF-100 significantly inhibited the CaCl2 dose response in high-K+ depolarizing medium. DF-100 inhibited the phasic contractile response to norepinephrine and the caffeine-induced response, suggesting that this molecule affects the mobilization of Ca2+ from a membrane-bound pool. In rat portal vein, DF-100 inhibited the spontaneous rhythmic contractions. The results obtained in this study in isolated rat aorta and portal vein suggest that DF-100 has a direct vasodilating effect that could be attributed to inhibition of cellular Ca2+ influx and release from intracellular stores.
DF - 100，即1 - 肼基 - 4 -（3,5 - 二甲基 - 1 - 吡唑基）- 5H - 哒嗪并[4,5 - b]吲哚，是一种与双肼屈嗪相关的新型哒嗪并[4,5 - b]吲哚衍生物。研究了DF - 100对离体主动脉和门静脉收缩的抑制作用。在大鼠主动脉中，DF - 100抑制钾离子诱导的收缩以及去甲肾上腺素诱导的收缩。DF - 100还引起由80 mM钾离子产生的收缩的剂量依赖性舒张。此外，DF - 100在高钾去极化介质中显著抑制氯化钙剂量反应。DF - 100抑制对去甲肾上腺素的相性收缩反应和咖啡因诱导的反应，表明该分子影响从膜结合池动员钙离子。在大鼠门静脉中，DF - 100抑制自发性节律性收缩。本研究在离体大鼠主动脉和门静脉中获得的结果表明，DF - 100具有直接的血管舒张作用，这可能归因于抑制细胞钙离子内流和从细胞内储存释放。
