Diazepam Enhances Fentanyl and Diminishes Meperidine Antinociception

摘要

A rabbit tooth pulp antinociceptive model was used to investigate the effect of prior administration of diazepam or muscimol on the potency and duration of fentanyl and meperidine Potency experiments compared ED50 values in all-or-none dose-response assays between both muscimol (0.25 mg/kg) and saline, and diazepam (1.5 mg/kg) and propylene glycol vehicle. An all-or-none effect was defined as doubling of voltage threshold to elicit a lick/chew evoked response. Duration experiments compared time (minutes) to 50% maximum possible effect (MPE) of an ED90 dose of fentanyl (0.04 mg/kg) and to 50% and 20% MPE of an ED98 dose of meperidine (17 mg/kg) 10 minutes after pretreatment with diazepam (1.5 mg/kg). Prior (10 minutes) injection of diazepam (1.5 mg/kg) increased the ED50 value for meperidine (3.06 mg/kg) compared with its control (1.48 mg/kg), indicating a decrease in antinociceptive potency. The same dose of diazepam decreased the ED50 value for fentanyl (1.1 μg/kg) compared with its control (13.1 μg/kg), indicating an increase in antinociceptive potency. Muscimol also had a similar effect on fentanyl (ED50, 1.8 μg/kg) compared with saline control (ED50, 13.8 μg/kg). Diazepam, vehicle, and muscimol by themselves had no effect on voltage thresholds to elicit a lick/chew response. Time to 50% MPE for diazepam-fentanyl was 38 minutes vs. 25 minutes for vehicle-fetanyl; time to 20% MPE for diazepam-meperidine was 38 minutes vs. 54 minutes for vehicle-meperidine (maximum percentage of MPE produced by diazepam-meperidine was 40% compared with 100% MPE for vehicle-meperidine). Percentages of MPE for diazepam-meperidine were significantly lower than those for vehicle-meperidine at all time intervals, whereas percentages of MPE for diazepam-fentanyl were significantly greater than those for vehicle-fentanyl over time.