Singh Y N, Johnson A, Lulf L A, Singh B N
College of Pharmacy, South Dakota State University, Brookings, USA.
Methods Find Exp Clin Pharmacol. 1996 Oct;18(8):499-506.
The effects of the calcium channel blocker isradipine were studied in the indirectly and directly stimulated mouse diaphragm and in the anesthetized rat to determine its potency, reversibility and interaction with a number of drugs. Initially, it potentiated both indirect and direct twitches followed by a reduction. With tetanic contractions, no potentiation was obtained, only a reduction, which was complete or near complete at the highest concentration tested (10(-4) M). In combination, isradipine reduced the IC50 and IC90 values for the antibiotics gentamicin, polymyxin B and clindamycin, d-rubocurarine and magnesium ions. Depression of contraction caused by isradipine or in combination could be reversed to varying degrees by washout, elevated calcium ions, neostigmine or 4-aminopyridine. Spontaneous recovery from the effects of isradipine alone or in combination was slow and usually incomplete. For in vivo experiments, severe cardiovascular depressant effects of isradipine limited its exposure to lower concentrations and for shorter periods. Under these conditions, it had no effect on heart rate. However, both systolic and diastolic blood pressure were significantly reduced, while pulse pressure was increased. After an initial potentiation muscle contraction was maximally reduced to 55% of control. This study indicates that acute administration of isradipine may aggravate neuromuscular effects of antibiotics, muscle relaxants or hypermagnesemia, although it is unlikely that spontaneous recovery or reversibility of muscular activity by suitable reversal agents will be affected. However, prolonged use of the drug may be more difficult to reverse.
研究了钙通道阻滞剂伊拉地平对间接和直接刺激的小鼠膈肌以及麻醉大鼠的作用，以确定其效力、可逆性以及与多种药物的相互作用。最初，它增强了间接和直接抽搐，随后出现减弱。对于强直收缩，未观察到增强作用，仅出现减弱，在测试的最高浓度（10⁻⁴ M）时减弱完全或接近完全。联合使用时，伊拉地平降低了抗生素庆大霉素、多粘菌素B和克林霉素、d - 筒箭毒碱和镁离子的IC50和IC90值。伊拉地平单独或联合使用引起的收缩抑制可通过冲洗、升高钙离子、新斯的明或4 - 氨基吡啶在不同程度上逆转。单独或联合使用伊拉地平后的自发恢复缓慢且通常不完全。对于体内实验，伊拉地平严重的心血管抑制作用限制了其暴露于较低浓度且时间较短。在这些条件下，它对心率没有影响。然而，收缩压和舒张压均显著降低，而脉压增加。在最初的增强作用后，肌肉收缩最大程度降低至对照的55%。本研究表明，急性给予伊拉地平可能会加重抗生素、肌肉松弛剂或高镁血症的神经肌肉效应，尽管合适的逆转剂对肌肉活动的自发恢复或可逆性不太可能产生影响。然而，长期使用该药物可能更难逆转。
