Effect of Phenobarbital Derivatives on the Duration of Hexobarbital Hypnosis

Meta-, and p-substituted nitro-, amino-, dimethylamino-, diethylamino-, hydroxy-, methoxy-, chloro- and fluoro-phenobarbital were synthesized. The shortening effect of these compounds, prominal, hexobarbital and α-3-hydroxyhexobarbital on the duration of hexobarbital hypnosis in rats was compared with that of phenobarbital. Meta-, and p-chloro- and fluoro-phenobarbital, prominal and phenobarbital showed the most potent shortening effect among above all compounds. Para-hydroxyphenobarbital and α-3-hydroxyhexobarbital, the hydroxylated metabolite of phenobarbital and hexobarbital, respectively, were less effective stimulator. Para-substituted nitro-, amino-, dimethylamino- and diethylamino-phenobarbital exhibited no stimulation, while corresponding m-derivatives and m- and p-methoxy-phenobarbital showed certain activities. Pretreatment of rats with m-chlorophenobarbital also markedly activated the metabolism of hexobarbital in vitro.