[Characteristics of the development of tolerance to nitrazepam and phenobarbital under experimental conditions]

Despite the similarity of the nitrazepam and phenobarbital spectra it was found that with their single usage the nature of tolerance for these substances differs quite substantially. With long-term introduction of nitrazepam to mice and rats in invariable and increasing doses there is seen a development of tolerance in the sense of the muscle relaxant and anticonvulsive action and in lethality without any marked attenuation of the tranquillizing effect. In contradistinction to this a long-term administration of phenobarbital is followed by a diminution of its tranquillizing action and by a slowly proceeding reduction of muscle relaxing manifestations. Crosswise tolerance among nitrazepam, diazepam and phenobarbital is marked but feebly. It is presumed that one of the possible mechanisms responsible for the nitrazepam tolerance in mice and rats may be a change in metabolic transformations and redistribution of metabolites.