氟西汀的神经肌肉阻断作用及其与罗库溴铵的相互作用

Autonomic and Autacoid Pharmacology Pub Date : 2013-03-06 DOI:10.1111/aap.12005

J. C. Patel, M. J. Barvaliya, T. K. Patel, C. B. Tripathi

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引用次数: 4

摘要

选择性5 -羟色胺再摄取抑制剂对烟碱乙酰胆碱受体具有抑制作用，可能影响神经肌肉传递并与神经肌肉阻滞剂相互作用。本研究采用大鼠膈神经半膈和兔头滴法观察氟西汀对神经肌肉传递的影响及其与罗库溴铵的相互作用。采用四脉冲(TOF)刺激大鼠膈神经半膈。通过绘制累积剂量反应曲线(DRCs)，研究氟西汀对间接和直接刺激的基底抽搐反应的影响。分别在5 μm和20 μm氟西汀不存在、不存在的情况下获得了罗库溴铵的DRCs，研究了其相互作用。计算不含氟西汀和不含氟西汀时罗库溴铵DRCs的ED5、ED50和ED95值。氟西汀在间接和直接刺激制剂中均显著抑制抽搐反应。氟西汀(20 μm)增加了罗库溴铵的效价，使罗库溴铵DRCs的ED50和ED95值显著降低。氟西汀(100 μm)部分抑制抽搐反应，新斯的明(3.3 μm)或3,4二氨基吡啶(0.25 μm)不能逆转抽搐反应。兔分别口服氟西汀0.25 mg kg - 1和1 mg kg - 1，连续15 d，第15 d滴注罗库溴铵，记录滴头时间。氟西汀预处理组与对照组相比，头部下降时间明显缩短。氟西汀阻断神经肌肉传导，增加罗库溴铵诱导的神经肌肉阻滞的效力。

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Neuromuscular blocking effect of fluoxetine and its interaction with rocuronium

As selective serotonin reuptake inhibitors have an inhibitory effect on nicotinic acetylcholine receptors, they may affect the neuromuscular transmission and interact with neuromuscular blockers. This study was designed to observe the effect of fluoxetine on neuromuscular transmission and its interaction with rocuronium using the rat phrenic nerve hemidiaphragm and rabbit head drop methods.
Rat phrenic nerve hemidiaphragms were mounted and stimulated using a train of four pulses (TOF). The effect of fluoxetine was studied on both indirectly and directly stimulated basal twitch responses by plotting cumulative dose response curves (DRCs). DRCs of rocuronium were obtained in the absence, and presence of 5 μm and 20 μm fluoxetine to study its interaction. ED₅, ED₅₀ and ED₉₅ values of rocuronium DRCs in absence and presence of fluoxetine were calculated.
Fluoxetine significantly inhibited twitch responses in both indirect and directly stimulated preparations. Fluoxetine (20 μm) caused an increase in the potency of rocuronium such that the ED₅₀ and ED₉₅ values of rocuronium DRCs were significantly decreased. Partially inhibited twitch responses by fluoxetine (100 μm) were not reversed by neostigmine (3.3 μm) or 3,4 diaminopyridine (0.25 μm).
Rabbits were given fluoxetine 0.25 mg kg⁻¹ and 1 mg kg⁻¹ orally for 15 days, and on 15th day, rocuronium infusion was given, and time for head drop was recorded. The time of head drop was significantly reduced in fluoxetine pretreated as compared to control group.
Fluoxetine blocks the neuromuscular transmission and increases the potency of rocuronium-induced neuromuscular block.

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