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.