Comparison of clonidine with fentanyl on phrenic nerve activity and their interaction in anaesthetized rabbits

We have compared the effects of clonidine and fentanyl on phrenic nerve activity in anaesthetized rabbits during artificial ventilation. Both drugs caused dose-dependent inhibition of phrenic nerve activity and complete abolition in all experiments. The calculated ED50 values were 3.7 micrograms kg-1 for clonidine and 3.9 micrograms kg-1 for fentanyl. Pretreatment with clonidine 1 microgram kg-1 i.v. depressed phrenic nerve activity to 81.8% of control values. This effect was additive with subsequent doses of fentanyl which was confirmed with an ED50 isobologram. We conclude that clonidine has the potential for deleterious respiratory effects at doses similar to those of fentanyl, but the interaction between the two drugs is additive and hence differs from their known synergistic antinociceptive interaction.