Interaction of local anaesthetic agents with the endogenous norepinephrinetransporter 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 anaesth etic inhibits uptake of guanethidine and hence reduces its efficacy. In thi s study we have examined the effects of a range of local anaesthetic agents on the uptake of [H-3]norepinephrine ([3H]NE) (as a surrogate for guanethi dine) and the binding of [H-3]nisoxetine to the NE transporter in cultured SH-SY5Y human neuroblastoma cells. All local anaesthetic agents inhibited N E uptake with a rank order cocaine > tetracaine > procaine(esters), dibucai ne > bupivacaine > prilocaine > lidocaine (amides). In addition all anaesth etic agents displaced [H-3]nisoxetine with a rank order cocaine > tetracain e > dibucaine > procaine > prilocaine > bupivacaine > lidocaine. There was a positive correlation between [H-3]NE uptake and [H-3]nisoxetine binding. Our data suggest that when local anaesthetic and guanethidine are co-admini stered the former may reduce uptake of the latter a nd hence reduce the cli nical efficacy of guanethidine. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.