Toxicity of 1-phenylcyclohexene and its interaction with phencyclidine.
The toxicity of 1-phenylcyclohexene (PC), a pyrolysis product of phencyclidine (PCP), and its interaction with PCP were evaluated. The ip LD50 of PC in Swiss male mice was 22 mmol/kg. Treatment of mice with PC at 2.2 mmol/kg/day, ip, for up to 7 days increased the liver/body weight ratio, which returned to normal within 7 days after PC withdrawal. Increases of 32% in serum glutamic-oxalacetic transaminase (SGOT) and 94% in serum glutamic-pyruvic transaminase (SGPT) were observed within 4 hr following the initial (Day 1) dose of PC. Smaller increases in the SGOT activity continued following Day 2 and 3 PC administrations. The SGPT activity remained elevated after these treatments. Activities of both enzymes, however, returned to normal within 24 hr following daily PC injections. No pathologic changes were observed in liver, brain, spleen, kidneys, and lungs with light microscopy. PC treatment for 4 days at 2.2 or 4.4 mmol/kg produced proliferation along with dilatation and fragmentation of the endoplasmic reticulum in liver. Scattering of ribosomes in the cytoplasm and dilatation of rough-surfaced cisternae were prominent at the higher dosage. Pretreatment of animals for 4 days with PC (1.1, 2.2, and 4.4 mmol/kg, ip) decreased pentobarbital- (60 mg/kg) induced sleeping time by 27, 64, and 80% and lowered PCP- (16.4 mumol/kg) stimulated locomotor activity by 18, 28, and 41%, respectively. Pretreatment of animals with PC for 1 hr inhibited (ED50: 2.3 mmol/kg) the PCP-induced locomotion. These results indicate that the PC treatment during a 7-day period produces some undesirable effects on liver function, which are reversible on its discontinuation. However, PC also weakens toxic effects of PCP.
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003510:Cyclohexanes / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D007928:Lethal Dose 50; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000648:ultrastructure; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D010622:Phencyclidine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010634:Phenobarbital / Q000378:metabolism; D012890:Sleep / Q000187:drug effects
D003510:Cyclohexanes; C034672:1-phenylcyclohex-1-ene; D005978:Glutathione; D010622:Phencyclidine; D010634:Phenobarbital