[The effects of flumazenil or bicuculline on the respiratory depression by morphine].
The effects of intravenous administration of flumazenil (n = 6) or bicuculline (n = 6) on the discharge of the phrenic nerve were studied following vagotomy in pentobarbital anesthetized mechanically ventilated rats. Morphine (0.4 mg.kg-1.min-1) was administrated until the respiratory rate decreased to about a half of the baseline respiratory rate. In this state, we first administered flumazenil (0.25 mg.kg-1) or bicuculline (0.4 mg.kg-1), intravenously and then administered naloxone (0.02 mg) intravenously in the two groups. The increase of inspiratory time from 0.7 +/- 0.1 to 2.0 +/- 0.5 s by morphine recovered to 0.8 +/- 0.2 s by bicuculline and to 0.6 +/- 0.1 s by naloxone. The increase of inspiratory time from 0.7 +/- 0.1 to 1.7 +/- 0.3 s by morphine, and to 2.1 +/- 0.5 s by flumazenil recovered to 0.6 +/- 0.1 s by naloxone. Expiratory time did not change during each drug administration in the two groups. The decrease of respiratory rate from 44 to 23 +/- 4 breaths.min-1 by morphine recovered to 37 +/- 5 breaths.min-1 by bicuculline and to 42 +/- 2 breaths.min-1 by naloxone. The decrease of respiratory rate from 45 +/- 3 to 22 +/- 6 breaths.min-1 by morphine, and to 18 +/- 4 breaths.min-1 by flumazenil recovered to 46 +/- 3 breaths.min-1 by naloxone. Amplitude of integrated phrenic nerve discharge increased to 125 +/- 42% by bicuculline and to 175 +/- 93% by naloxone compared to the baseline values. The decrease of amplitude to 54 +/- 18% by flumazenil recovered to 125 +/- 42% by naloxone. These results suggest that bicuculline not flumazenil antagonizes the respiratory depression of morphine by increasing the respiratory rate and respiratory movement.
Kasaba
T
T
Department of Anesthesiology, Miyazaki Medical College.
Takeshita
M
M
Takasaki
M
M
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology*; D003864:Depression, Chemical; D005442:Flumazenil / Q000494:pharmacology*; D018756:GABA Antagonists / Q000494:pharmacology*; D018757:GABA Modulators / Q000494:pharmacology*; D009020:Morphine / Q000037:antagonists & inhibitors*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010791:Phrenic Nerve / Q000187:drug effects; D051381:Rats; D012119:Respiration / Q000187:drug effects*; D012131:Respiratory Insufficiency / Q000139:chemically induced
D018756:GABA Antagonists; D018757:GABA Modulators; D009292:Narcotic Antagonists; D009270:Naloxone; D005442:Flumazenil; D009020:Morphine; D001640:Bicuculline