Interaction of local anaesthetic agents with the endogenous norepinephrine transporter in SH-SY5Y human neuroblastoma cells.
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.
Joyce
P I
PI
University Department of Anaesthesia Critical Care and Pain Management, Leicester Royal Infirmary, LE1 5WW, Leicester, UK.
Atcheson
R
R
Marcus
R J
RJ
Heffernan
A M
AM
Rowbotham
D J
DJ
Lambert
D G
DG
D000779:Anesthetics, Local / Q000494:pharmacology*; D002352:Carrier Proteins / Q000187:drug effects* / Q000378:metabolism; D005473:Fluoxetine / Q000031:analogs & derivatives / Q000378:metabolism; D006801:Humans; D009638:Norepinephrine / Q000493:pharmacokinetics; D050484:Norepinephrine Plasma Membrane Transport Proteins; D027981:Symporters; D014407:Tumor Cells, Cultured
D000779:Anesthetics, Local; D002352:Carrier Proteins; D050484:Norepinephrine Plasma Membrane Transport Proteins; C493227:SLC6A2 protein, human; D027981:Symporters; D005473:Fluoxetine; C011386:nisoxetine; D009638:Norepinephrine