Fentanyl inhibits the uptake of [3H]noradrenaline in cultured neuronal cells.

We have examined how fentanyl modulates [3H]noradrenaline uptake in two cultured neuronal cell preparations, the human neuroblastoma SH-SY5Y and the rat phaeochromocytoma PC12. Fentanyl produced a significant, dose-dependent inhibition of [3H]noradrenaline uptake at concentrations in excess of 0.1 mumol litre-1 (P < 0.05) and 0.3 mumol litre-1 (P < 0.05) for PC12 and SH-SY5Y cells, respectively. However, these values exceed the serum concentration of fentanyl required to produce analgesia. At the maximum concentration examined (100 mumol litre-1), fentanyl produced 85-95% inhibition of uptake. This effect was not antagonized by naloxone, implying a nonopioid mechanism of action. Imipramine 1 mumol litre-1 reduced [3H]noradrenaline uptake by 65-70% but morphine, in contrast to fentanyl, had no effect (P > 0.1).