Neuromuscular blocking effect of fluoxetine and its interaction with rocuronium

Abstract

1. 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.
2. 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.
3. 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).
4. 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.
5. Fluoxetine blocks the neuromuscular transmission and increases the potency of rocuronium-induced neuromuscular block.