Antagonism of the effects of midazolam on phrenic nerve activity in the dog by Ro 15-1788 and Ro 15-3505.

Experiments were performed on 14 anaesthetized, artifically ventilated dogs, in which efferent activity in the phrenic nerve was recorded and blood-gas tensions, arterial pH and core temperature were controlled. Doses of midazolam between 0.2 mg kg-1 and 2 mg kg-1 abolished phrenic nerve activity for periods between 30 and 90 min. Ro 15-1788 in doses between 0.06 mg kg-1 and 1 mg kg-1 and Ro 15-3505 0.2-2 mg kg-1 reversed the effects of midazolam on phrenic nerve activity. Prior administration of these drugs either abolished or greatly inhibited the action of midazolam. When the preparations were observed for up to 2 h, there was no evidence of return of the action of midazolam, suggesting that both antagonists had a duration of action at least as long as that of midazolam.