Block of neuronal tetrodotoxin-resistant Na+ currents by stereoisomers of piperidine local anesthetics.

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Brau ME, Branitzki P, Olschewski A, Vogel W, Hempelmann G

Block of neuronal tetrodotoxin-resistant Na+ currents by stereoisomers of piperidine local anesthetics.

Anesth Analg. 2000 Dec;91(6):1499-505.

PubMed ID

11094008 [ View in PubMed

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Abstract

Tetrodotoxin (TTX)-sensitive Na(+) channels in the peripheral nervous system are the major targets for local anesthetics. In the peripheral nociceptive system, a Na(+) channel subtype resistant to TTX and with distinct electrophysiological properties seems to be of importance for impulse generation and conduction. A current through TTX-resistant Na(+) channels displays slower activation and inactivation kinetics and has an increased activation threshold compared with TTX-sensitive Na(+) currents and may have different pharmacological properties. We studied the effects of stereoisomers of piperidine local anesthetics on neuronal TTX-resistant Na(+) currents recorded with the whole-cell configuration of the patch clamp method in enzymatically dissociated dorsal root ganglion neurons of adult rats. Stereoisomers of mepivacaine, ropivacaine, and bupivacaine reversibly inhibited TTX-resistant Na(+) currents in a concentration and use-dependent manner. All drugs accelerated time course of inactivation. Half-maximal blocking concentrations were determined from concentration-inhibition relationships. Potencies for tonic and for use-dependent block increased with rising lipid solubilities of the drugs. Stereoselective action was not observed. We conclude that block of TTX-resistant Na(+) currents may lead to blockade of TTX-resistant action potentials in nociceptive fibers and consequently may be responsible for pain suppression during local anesthesia.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Levobupivacaine	Sodium channel protein type 10 subunit alpha	Protein	Humans	Yes	Inhibitor	Details