1,4-Benzodiazepines antagonize opiate-induced antinociception in mice.
The influence of diazepam, midazolam, and flunitrazepam on the antinociceptive effect of morphine, fentanyl, and buprenorphine was studied using the hot-plate test and the tail-flick test in mice. Diazepam and midazolam induced a dose-dependent attenuation of the effect of all three opiates in both tests of nociception. Flunitrazepam antagonized the antinociceptive effect only in the tail-flick test. The benzodiazepine effect could not be explained by altered tail-skin temperature. The antagonism did not correlate well with the sedative or muscle-relaxing properties of the benzodiazepines, and a different mechanism may therefore be involved. It is proposed that the antagonism represents an interaction between benzodiazepines and opioid systems in the brain participating in modulation of nociceptive inputs.
Rosland
J H
JH
Department of Physiology, University of Bergen, Norway.
Hole
K
K
D000698:Analgesia; D000818:Animals; D002047:Buprenorphine / Q000037:antagonists & inhibitors; D003975:Diazepam / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005283:Fentanyl / Q000037:antagonists & inhibitors; D005445:Flunitrazepam / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008874:Midazolam / Q000494:pharmacology*; D009020:Morphine / Q000037:antagonists & inhibitors; D009292:Narcotic Antagonists / Q000494:pharmacology*; D011597:Psychomotor Performance / Q000187:drug effects
D009292:Narcotic Antagonists; D002047:Buprenorphine; D005445:Flunitrazepam; D009020:Morphine; D003975:Diazepam; D008874:Midazolam; D005283:Fentanyl