Leeuwin R S, Zeegers A, Van Wilgenburg H
Department of Pharmacology, University of Amsterdam, The Netherlands.
Eur J Pharmacol. 1996 Nov 14;315(2):153-7. doi: 10.1016/s0014-2999(96)00603-6.
Diazepam (2 x 10(-5)-6 x 10(-4) M) induced a concentration-dependent positive inotropic effect on the perfused rat heart which was preceded by a transient concentration-dependent negative inotropic response. The influence of the Ca(2+)-entry blocking drug, flunarizine, and the adenosine receptor blocking drug, theophylline on these inotropic responses was studied. Flunarizine in concentrations of 10(-9)-10(-6) M antagonized the positive inotropic response to diazepam significantly; the negative inotropic response was reduced as well. At the lower concentrations of diazepam the negative inotropic response was completely abolished in the presence of flunarizine. The actions of the Ca(2+)-entry blocker were related to the concentrations used. Theophylline in concentrations up to 5 x 10(-5) M did not interfere with either inotropic response to diazepam. The results suggest that Ca2+ currents in the myocardium are involved with the response of the isolated heart to diazepam. It is concluded that the finding that the negative inotropic effect of diazepam was almost abolished by flunarizine suggests that the site of this response most be associated with Ca(2+)-current mechanisms.
地西泮（2×10⁻⁵ - 6×10⁻⁴ M）对灌注大鼠心脏产生浓度依赖性的正性肌力作用，在此之前有短暂的浓度依赖性负性肌力反应。研究了钙通道阻滞药氟桂利嗪和腺苷受体阻滞药茶碱对这些肌力反应的影响。浓度为10⁻⁹ - 10⁻⁶ M的氟桂利嗪显著拮抗地西泮的正性肌力反应；负性肌力反应也有所降低。在较低浓度的地西泮作用下，氟桂利嗪存在时负性肌力反应完全消失。钙通道阻滞剂的作用与所用浓度有关。浓度高达5×10⁻⁵ M的茶碱不干扰地西泮的任何一种肌力反应。结果表明，心肌中的钙电流与离体心脏对地西泮的反应有关。得出结论，氟桂利嗪几乎消除地西泮的负性肌力作用这一发现表明，该反应的部位很可能与钙电流机制有关。
