The role of hepatic microsomal enzymes in the modulation of phencyclidine-induced toxicity.
The LD50 of phencyclidine (PCP, 234 mumol/kg, i.p.) in male Swiss mice decreased by 62% in animals pretreated with 2-diethylamino-2,2-diphenylvalerate hydrochloride (SKF-525A, 40 mg/kg), and increased by 74% and 20% in animals pretreated with sodium phenobarbital (75 mg/kg), and 3-methylcholanthrene (70 mg/kg), respectively, No Significant change in the LD50 was observed with cysteine or diethylmaleate pretreatment. The treatment with PCP at 179 mumol/kg/day i.p. for 7 days resulted in body weight decrement in the first 2 days and gradual increment thereafter. The increase was only 33% of the control group. The food intake was also lower in the PCP treated group of animals. PCP withdrawal led to an increase in food intake as well as body weight at a normal rate. The ratio of liver weight to body weight was not significantly higher than that of control during the treatment period. The administration of PCP for 7 days did not alter the activities of liver function enzyme markers. However, within 12 h of the initial PCP treatment a 85% increase in activity of serum glutamicoxalacetic transaminase was observed. Later the enzyme activity reached close to normal levels. No liver lesions at the light microscopic level were observed. Treatment of mice for 4 days with PCP (179 mumol/kg) caused no significant change in pentobarbital sleeping time.
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003545:Cysteine / Q000494:pharmacology; D004435:Eating / Q000187:drug effects; D007928:Lethal Dose 50; D008099:Liver / Q000187:drug effects; D008297:Male; D008298:Maleates / Q000494:pharmacology; D008748:Methylcholanthrene / Q000494:pharmacology; D051379:Mice; D008862:Microsomes, Liver / Q000201:enzymology*; D010424:Pentobarbital / Q000378:metabolism; D010622:Phencyclidine / Q000378:metabolism / Q000633:toxicity*; D010634:Phenobarbital / Q000494:pharmacology; D011335:Proadifen / Q000494:pharmacology
D008298:Maleates; D008748:Methylcholanthrene; D011335:Proadifen; C014476:diethyl maleate; D010424:Pentobarbital; D010622:Phencyclidine; D003545:Cysteine; D010634:Phenobarbital