COMPARISON OF CLONIDINE WITH FENTANYL ON PHRENIC-NERVE ACTIVITY AND THEIR INTERACTION IN ANESTHETIZED RABBITS

We have compared the effects of clonidine and fentanyl on phrenic nerv e activity in anaesthetized rabbits during artificial ventilation. Bot h drugs caused dose-dependent inhibition of phrenic nerve activity and complete abolition in all experiments. The calculated ED(50) values w ere 3.7 mu g kg(-1) for clonidine and 3.9 mu g kg(-1) for fentanyl. Pr etreatment with clonidine 1 mu g kg(-1) i.v. depressed phrenic nerve a ctivity to 81.8% of control values. This effect was additive with subs equent doses of fentanyl which was confirmed with an ED(50) isobologra m. We conclude that clonidine has the potential for deleterious respir atory effects at doses similar to those of fentanyl, but the interacti on between the two drugs is additive and hence differs from their know n synergistic antinociceptive interaction.