Diazepam—Morphine Hypnotic Synergism in Rats

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Abstract
The effect of diazepam-morphine combination on the righting reflex was studied in rats. Doses of the drugs given alone an in combination that block righting reflex (RR ED50) were determined with a probit procedure. Brain concentrations following equieffective doses of the drugs administered separately and in combination were determined by radioimmunoassy. Equieffective intravenous doses and corresponding brain concentrations for the agents were compared with fractional (algebraic) and isobolographic analyses. Interaction between diazepam and morphine was found to be synergistic. It is not likely to be pharmacokinetic in nature.