Physostigmine is equipotent to flumazenil only in excessive doses, while naloxone is ineffective in reversing midazolam anesthesia
Sarlis, N.J.; Kaniaris, P.K.
Middle East Journal of Anaesthesiology 11(3): 271-288
1991
ISSN/ISBN: 0544-0440 PMID: 1815114 Document Number: 386210
As fast-acting, water-soluble compounds, like midazolam (MID) are increasingly used in anesthetic practice, the need for quick and effective reversal of benzodiazepine actions in accidental overdoses is obvious. Quite a few drugs have been used in both animal models and clinically towards this aim, including: physostigmine (PHYS), naloxone (NAL), aminophylline, doxapram, in the past and, more recently, flumazenil (FLU) or Ro-15-1788. In the present study we assessed the relative potency, safety and efficacy of the antagonistic actions of PHYS (0.06 and 0.6 mg/kg), NAL (2 mg/kg) and FLU (2.5 mg/kg) on the state of sleep induced by MID (2.5 mg/kg) in 50 male, drug-naive rats. Time of induction of anesthesia and duration of sleep were measured with digital chronometer. Level of consciousness was determined by pain reactivity, spontaneous motor activity and computer-aided analysis of cumulative EEG patterns. Times obtained were integrated as mean values and statistical analysis was made using the t-test (Student's criterion). Rats were given MID followed 30 min later by an i.p. injection of either vehicle (VEH = water for injection = control group) or low-dose PHYS or high-dose PHYS or NAL or FLU (n = 10 in each group). We measured the duration of anesthesia following the injection of each antagonist.