Abstract
A comparative study of 5,5'-diphenyl-2-thiohydantoin (DPTH), 5,5'-diphenylhydantoin and phenobarbital (PB) as inducers of microsomal drug-metabolizing enzymes has been made. DPTH caused a dose-related hepatomegaly in the rate associated with an increase in hepatic protein and lipid content. Hexobarbital sleeping time in the mouse was reduced by prior administration of DPTH. Oral administration of DPTH was superior to diphenylhydantoin and equal to PB in its ability to increase ethylmorphine N-demethylase activity in rat liver 10,000 x g supernatants. DPTH had equivalent activity to PB and diphenylhydantoin after i.p. injection. Liver microsomal protein and phospholipid content was increased by DPTH administration and electron micrographs of hepatocytes from treated rats showed a proliferation of the smooth endoplasmic reticulum. The onset of induction was similar for both DPTH and PB. Similar maximal effects were attained and reversal to normal values, after cessation of drug treatment, was the same for both DPTH and PB. Microsomal cytochrome P-450 content was elevated by DPTH treatment but little effect on cytochrome P-450 reductase activity was observed. Because of this DPTH may prove to be a more useful agent than PB in the study of the induction phenomenon in animals. In addition, although it has similar potency, DPTH has the advantage of having less side effects and of not being a hypnotic agent.
Footnotes
- Received January 26, 1972.
- Accepted May 24, 1972.
- © 1972 by The Williams & Wilkins Co.
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