Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Bräu, 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 91: 1499-1505.
Doi: 10.1097/00000539-200012000-00038
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- Co-Autor*innen der Med Uni Graz
- Olschewski Andrea
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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.
- Find related publications in this database (using NLM MeSH Indexing)
- Algorithms -
- Amides - pharmacology
- Anesthetics, Local - pharmacology
- Animals - pharmacology
- Bupivacaine - pharmacology
- Cells, Cultured - pharmacology
- Drug Resistance - pharmacology
- Mepivacaine - pharmacology
- Patch-Clamp Techniques - pharmacology
- Piperidines - pharmacology
- Rats - pharmacology
- Rats, Wistar - pharmacology
- Research Support, Non-U.S. Gov't - pharmacology
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- Sodium Channels - drug effects
- Stereoisomerism - drug effects
- Tetrodotoxin - pharmacology