The effects of flumazenil on the antinociceptive actions of morphine in rats.
The 8-fluoro-5,6-dihydro-5-methyl-6-oxo-4H-imidazol[1,5-a][1,4]benzodiazepine-3-carboxylic acid ethyl ester (Flumazenil)-morphine interaction on analgesia (acute pain model, tail-flick test) was tested after intraperitoneal (IP) and intrathecal (IT) routes of administration in female rats. Analgesia was enhanced by the concurrent administration of Flumazenil with morphine (IP), in a dose-related way. Flumazenil alone (IP) did not produce analgesia. In contrast, morphine analgesia was not enhanced by Flumazenil by the IT route. These data demonstrate that Flumazenil enhances morphine-mediated antinociception by mechanisms that are likely to involve benzodiazepine receptors at sites other than the spinal cord.
Holtman
Joseph R
JR
Department of Anesthesiology, College of Medicine, University of Kentucky, Lexington, Kentucky 40536-0296, USA. jrjr@uky.edu
Jing
Xin
X
Sloan
Jewell W
JW
Wala
Elzbieta P
EP
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001569:Benzodiazepines / Q000037:antagonists & inhibitors; D004347:Drug Interactions; D005260:Female; D005442:Flumazenil / Q000008:administration & dosage / Q000494:pharmacology*; D009020:Morphine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000701:Analgesics, Opioid; D001569:Benzodiazepines; D005442:Flumazenil; D009020:Morphine