Evidence of presynaptic and postsynaptic action of local anesthetics in rats

Abstract

PURPOSE:To assess the probable actions of ropivacaine, 50% enantiomeric excess bupivacaine mixture (S75-R25) and levobupivacaine on neuromuscular transmission in vitro. METHODS:Thirty rats were distributed into groups (n=5) according to the drug used: ropivacaine, bupivacaine (S75-R25) and levobupivacaine. The concentration used for the three local anesthetics (LA) was 5 µg.mL.-1 The following parameters were evaluated:1) LA effects on membrane potential (MP) and miniature end plate potential (MEPP). A chick biventer cervicis preparation was also used to evaluate LA effects on the contracture response to acetylcholine. RESULTS:LA did not alter MP values and decreased the frequency and amplitude of MEPP. In a chick biventer cervicis preparation, bupivacaine (S75-R25) and levobupivacaine decreased the contracture response to acetylcholine with statistical significance, in comparison to ropivacaine. CONCLUSIONS:In the concentrations used, levobupivacaine and bupivacaine (S75-R25) exhibited presynaptic and postsynaptic actions evidenced by alterations in miniature end plate potentials and contracture response to acetylcholine. Ropivacaine only had a presynaptic action.

Use of neuromuscular blockers and neostigmine for general anesthesia and its association with neuraxial blockade

“…In the postsynaptic region, local anesthetics lead to receptor desensitization, cause temporary occlusion of nicotinic receptor channels, and interfere in the process of excitation–contraction coupling of the muscle fiber. [42,43,46–49] Previous authors have found that neuraxial blockade can be related to reduction on the needed dose of NMB during GA or delayed recovery to TOF ratio of 0.9 when unchanged doses of NMB are administered. [45,47] These reports were prospective studies with smaller group of patients and with the aid of neuromuscular monitoring.…”

Association between levobupivacaine and pancuronium. Interference in neuromuscular transmission and blockade in rats

“…Presynaptic and postsynaptic events have been described [1][2][3][4]9,10 . To identify the probable mechanism of interaction and potentiation of the block produced by pancuronium, in a preparation previously exposed to levobupivacaine, electrophysiological studies were conducted.…”

“…In the evaluation of bioelectrical potentials, it was observed that levobupivacaine, in the concentration employed, did not alter the membrane potential of muscle fibers, which remained within normal limits (-85 mV). It was demonstrated that the drug has no depolarizing action on skeletal muscle fibers, although it prevents the conduction of action potentials 4 .…”

“…To explain the interaction between local anesthetics and neuromuscular blocking agents, several mechanisms have been described, including a presynaptic action by inhibition of acetylcholine release, a postsynaptic action due to stabilization of the postjunctional membrane, and interference with the phenomenon of excitation-contraction coupling of the muscle fiber [1][2][3][4] . Although only high concentrations of local anesthetics can produce neuromuscular blockade, the interaction between these drugs and nondepolarizing neuromuscular blocking agents in particular is relevant in clinical practice, when both groups of drugs are used simultaneously and careful patient monitoring is required.…”

“…that has a lower lipid solubility, lower cardiotoxicity and neurotoxicity, a greater sensory blockade and less profound motor blockade than racemic bupivacaine 4,6 . Pancuronium is a longacting aminosteroid, nondepolarizing neuromuscular blocking agent, used in prolonged surgeries and in intensive care units 1 .…”