Synergistic interaction of 4-aminopyridine with neostigmine at the neuromuscular junction.
Synergistic interaction of 4-aminopyridine with neostigmine at the neuromuscular junction.
复制标题
4-氨基吡啶与新斯的明在神经肌肉接头处的协同相互作用。
DOI：
10.1016/0014-2999(85)90696-x
复制
发表时间：
1985
影响因子：
5
通讯作者：
Johns,TR
中科院分区：
文献类型：
--
作者：
Tierney,PC;Kim,YI;Johns,TR
在体外研究了暴露于临床显著浓度的4-氨基吡啶（4-AP）、新斯的明或两种药物联合的大鼠骨骼肌神经肌肉接头处的突触前和突触后事件。同时应用4-AP和新斯的明产生的神经诱发终板电位的幅度增加，这是显着大于单独应用的药物的总和的影响。这种协同作用存在于突触后被d-筒箭毒碱阻断或突触前被低[Ca 2 +] 0和高[Mg 2 +] 0阻断的连接处。在后者的制备量子含量分析表明，诱发释放乙酰胆碱的增强显着超过自发的微型终板电位的幅度，这表明协同作用的网站主要是突触前。对于症状缓解和长期管理的神经肌肉接头疾病，我们建议在减少剂量的氨基吡啶和抗胆碱酯酶联合用药。这种疗法将使副作用最小化，并且在治疗诸如Lambert-Eaton肌无力综合征和肉毒杆菌中毒的突触前疾病中特别有效。
The pre- and postsynaptic events at the neuromuscular junction were studied in vitro in rat skeletal muscle exposed to clinically significant concentrations of 4-aminopyridine (4-AP), neostigmine or combinations of the two drugs. Simultaneous application of 4-AP and neostigmine produced increases in the amplitudes of nerve-evoked end-plate potentials which were significantly greater than the summed effects of the drugs applied individually. Such synergism was present at the junctions where transmission was blocked either postsynaptically by d-tubocurarine or presynaptically by low [Ca2+]0and high [Mg2+0. Quantal content analysis in the latter preparation indicated that the evoked release of acetylcholine was potentiated significantly more than the amplitude of spontaneous miniature end-plate potentials, suggesting that the site of synergism is predominantly presynaptic. For symptomatic relief and long-term management of the neuromuscular junction disorders, we propose a combined medication of aminopyridine and anticholinesterase at reduced dosages. Such therapy would minimize adverse effects and be particularly effective in the treatment of such presynaptic disorders as the Lambert-Eaton myasthenic syndrome and botulism.