Attenuation of Pethidine‐induced Antinociception by Zimelidine, an Inhibitor of 5‐hydroxytryptamine Reuptake

1 The effect of selective inhibition of 5-hydroxytryptamine (5-HT) re-uptake by fluoxetine and zimelidine on morphine- and pethidine-induced antinociception was studied in rats. The hot plate (55 degrees C) and tail flick test procedures for measurement of analgesia were employed to assess antinociception. 2 Pretreatment with fluoxetine and zimelidine potentiated the antinociceptive effect of morphine (4.5 mg/kg, as base); zimelidine was without effect on a lesser dose of morphine (3.0 mg/kg, as base). 3 Pretreatment with zimelidine but not fluoxetine, significantly attenuated pethidine-induced antinociception (24 mg/kg, as base) and prevented the expression of pethidine-induced antinociception at a lesser 10 mg/kg (as base) dose of pethidine. 4 These and other results support (a) a role for 5-HT in the expression of morphine-induced antinociception, and (b) a different mode of antinociceptive action of morphine and pethidine. The role of 5-HT in pethidine-induced antinociception remains unclear.