Interaction of local anaesthetic agents with the endogenous norepinephrine transporter in SH-SY5Y human neuroblastoma cells.

Abstract

Use of intravenous guanethidine for the treatment of complex regional pain syndrome type I is of variable efficacy. Guanethidine injection is painful, so local anaesthetic is co-administered. We hypothesize that local anaesthetic inhibits uptake of guanethidine and hence reduces its efficacy. In this study we have examined the effects of a range of local anaesthetic agents on the uptake of [3H]norepinephrine ([3H]NE) (as a surrogate for guanethidine) and the binding of [3H]nisoxetine to the NE transporter in cultured SH-SY5Y human neuroblastoma cells. All local anaesthetic agents inhibited NE uptake with a rank order cocaine>tetracaine>procaine(esters), dibucaine > bupivacaine > prilocaine > lidocaine (amides). In addition all anaesthetic agents displaced [3H]nisoxetine with a rank order cocaine > tetracaine > dibucaine > procaine > prilocaine > bupivacaine > lidocaine. There was a positive correlation between [3H]NE uptake and [3H]nisoxetine binding. Our data suggest that when local anaesthetic and guanethidine are co-administered the former may reduce uptake of the latter and hence reduce the clinical efficacy of guanethidine.

• Authors: P I Joyce, R Atcheson, R J Marcus, A M Heffernan, D J Rowbotham, D G Lambert
• Journal: Neuroscience letters (Neurosci Lett) Vol. 305 Issue 3 Pg. 161-4 (Jun 15 2001) ISSN: 0304-3940 [Print] Ireland
• PMID: 11403930 (Publication Type: Journal Article)

Chemical References

• Anesthetics, Local
• Carrier Proteins
• Norepinephrine Plasma Membrane Transport Proteins
• SLC6A2 protein, human
• Symporters
• Fluoxetine
• nisoxetine
• Norepinephrine

Topics

• Anesthetics, Local (pharmacology)
• Carrier Proteins (drug effects, metabolism)
• Fluoxetine (analogs & derivatives, metabolism)
• Humans
• Norepinephrine (pharmacokinetics)
• Norepinephrine Plasma Membrane Transport Proteins
• Symporters
• Tumor Cells, Cultured