[Comparative studies of enzyme-inducing ability of phenobarbital, methylphenobarbital, glutethimide and their N-substituted morphoalkylic derivatives].
The authors examined the capability of N-substituted morpholinoalkyl derivated of phenobarbiral methylphenobarbital and glutetimide to induce drug-dissimilated enzymes in liver microsomes as those newly syntesized compounds were compared with the initial substances, which were enzyme inductors. They examined the following indices: duration of hexobarbital narcosis after a six day treatment of male white rats with one of the substances liver weight, related to the percentage of the whole body weight, protein content in liver homogenates and in microsomal fraction of liver, the activity of N-demetilase in liver. There was a considerable shortening of the duration of hexobarbital sleep due to barbiturates, more manifested in animals, treated with methylphenobarbital. Glutetimide shortened the narcosis statisticaly insignificant. The respective morpholonoalkylic derivatives not only did not shortened the narcotic sleep, but even slightly prolonged. it. The liver weight of the rats, treated with barbiturates, was increased with 25--30% while that of the rats treated with morpholinoalkylic derivatives did not differ from the liver weight of the control animals. The protein content in liver homogenates did not show statistically significant differences in the single groups. The protein content of the microsomal liver fraciton was increased in the animals, treated with barbiturates and glutetimide, while in the rats, treated with morphoalkylic derivatives the protein content did not differ from that of the controls, but it was even reduced after treatment with a derivative of glutetimide. Phenobarbital and methylphenobarbital increased significantly the activity of pyrimidone N-demetilase, while their N-substituted morpholinc-alkyli derivatives inhibited it.
D000818:Animals; D004790:Enzyme Induction / Q000187:drug effects; D005984:Glutethimide / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects; D008297:Male; D008618:Mephobarbital / Q000494:pharmacology*; D008862:Microsomes, Liver / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D010089:Oxidoreductases, N-Demethylating / Q000096:biosynthesis*; D010634:Phenobarbital / Q000494:pharmacology*; D051381:Rats; D013997:Time Factors
D008618:Mephobarbital; D005984:Glutethimide; D010089:Oxidoreductases, N-Demethylating; D010634:Phenobarbital
Sravnitelni prouchvaniia vurkhu enzim-indutsirashtata sposobnost na fenobarbitala, metilfenobarbitala, glutetimida i tekhnite N-substituirani morfolino-alkilni proizvodni.