Sex-dependent differences in the pharmacological actions and pharmacokinetics of phencyclidine in rats.
This study was designed to assess the sex differences in phencyclidine(PCP)-induced ambulatory activity in an open-field, stereotyped behaviors, motor incoordination, tremor, salivation, the regional and subcellular distributions of PCP in the brain and the half-life of PCP in the brain and plasma. Female rats appeared to be more sensitive to PCP as evidenced by hyperactivity, stereotyped behaviors, motor incoordination, tremor, salivation and ataxia. The concentrations of PCP in female rat brain were higher than in the male rats in some discrete brain areas and subcellular fractions. The half-life of PCP in the brain and plasma was longer in female rats than in male rats. The inverse relationship of pharmacological responses to PCP and biotransformation of PCP in both sexes of rats suggests that sex differences in pharmacological actions of PCP depend largely on differences in ability to biotransform the drug.
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001711:Biotransformation; D001921:Brain / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005260:Female; D006207:Half-Life; D006801:Humans; D007700:Kinetics; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D010622:Phencyclidine / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012472:Salivation; D012737:Sex Factors; D013239:Stereotyped Behavior / Q000187:drug effects*; D014202:Tremor / Q000139:chemically induced
D003577:Cytochrome P-450 Enzyme System; D010622:Phencyclidine