Effect of 1-(m-chlorophenyl)-3-N,N-dimethyl-carbamoyl-5-methoxypyrazole (PZ-177) on drug-metabolizing enzyme on rat liver.
Effect of 1-(m-chlorphenyl)-3-N,N-dimethylcarbamoyl-5-methoxypyrazole (PZ-177) (62.5 and 250 mg/kg) on rat liver was investigated by measuring liver weight and drug-metabolizing enzyme activity. The effects of PZ-177 were compared with those of phenobarbital, phenylbutazone, and tiaramide hydrochloride. Increase of liver weight and liver/body weight ratio was observed in the rats treated with PZ-177 or phenobarbital, however, normal values were reverted to 1--2 weeks after treatment. PZ-177 similar to phenobarbital, significantly enhanced the activity of aminopyrine demethylase and aniline hydroxylase after 1,2, and 4 weeks of treatment. In contrast, tiaramide hydrochloride decreased the activity of aminopyrine demethylase and aniline hydroxylase after 1 week of treatment, and significantly enhanced the activity of these enzymes after 4 weeks. The content of cytochrome P-450 and the activity of NADPH cytochrome C reductase were also increased by treatment with PZ-177. The sleeping time by hexobarbital was shortened significantly by the administration of PZ-177. Vmax for both aminopyrine demethylase and aniline hydroxylase increased by treatment with PZ-177. However, only the Km for aniline hydroxylase was increased by treatment with PZ-177. From the results of these experiments, PZ-177 may be classified as a phenobarbital-type inducer.
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D052160:Benzothiazoles; D001835:Body Weight / Q000187:drug effects; D004790:Enzyme Induction; D007700:Kinetics; D008099:Liver / Q000033:anatomy & histology / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010634:Phenobarbital / Q000494:pharmacology; D010653:Phenylbutazone / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology*; D051381:Rats; D013844:Thiazoles / Q000494:pharmacology; D013997:Time Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052160:Benzothiazoles; D010879:Piperazines; D011720:Pyrazoles; D013844:Thiazoles; C011584:PZ 177; C003468:tiaramide; D010653:Phenylbutazone; D010634:Phenobarbital