ACUTE "TOLERANCE" TO THE CENTRAL RESPIRATORY EFFECTS OF MIDAZOLAM IN THE DOG

The effect of repeated doses of midnTinlam 0.1 mg kg^–1on efferent activity in the phrenic nerve was observed in sevenartificially ventilated dogs, anaesthetized with chloraloseand paralysed with suxamethonium. PaO₂, .PaCo₂ arterial pH andcore temperature were adjusted to constant values throughouteach experiment. The first dose of midazolam caused a relativelyprolonged reduction in phrenic activity, after complete recoverya second dose was administered and so on for four doses. Peakphrenic efferent activity returned to initial values on average69 4min after the first dose of miHnTnlam The effects of successivesubsequent doses lasted progressively shorter times (mean values49.4, 38.7 and 25.3min). In four preparations, 2 h after recoveryfrom the fourth doses a second "train" of four doses was administered.The response to the first dose of this second "train" showedthat 90% recovery had occurred from the effect of the first"train" and there wts a similar sequence of decreasing responsesto successive doses. This study demonstrated acute toleranceto the central respiratory effects of midazolam. ^*Present address: Department of Anaesthetics, Brompton Hospital,Fulham Road, London SW3 6HP.