A survey of the response of different strains of mice to substances metabolised by microsomal oxidation; hexobarbitone, zoxazolamine and warfarin.
Sixteen strains of mice were compared with respect to their hexobarbitone sleeping time and their zoxazolamine paralysis time. The strains were A2G, CBA, CE, C3H, C57BL, C57L, DBA, F/st, ICFW, NMRI, NZB, Schneider, Simpson, SM, TO and 129/rr. All the strains except 129 Rr were also tested for survival on a diet containing 0.05% racemic Warfarin. There was highly significant interstrain correlation between hexobarbitone sleeping time and zoxazolamine paralysis time (r = 0.72) and between hexobarbitone sleeping time Warfarin survival (r = 0.68). There was a significant correlation between zoxazolamine paralysis time and Warfarin survival (r = 0.56). The correlations can be explained if: (1) there is a genetically determined interstrain variable which is some common component of the microsomal mixed-function oxidase systems involved in the hydroxylation of the three substances; (2) the anticoagulant action of Warfarin is caused more by a hydroxylated metabolite of Warfarin than by Warfarin itself. Phenobarbitone pretreatment shortened hexobarbitone sleeping times and zoxazolamine paralysis times, but its effect was greater in those strains with longer initial hexobarbitone sleeping times and zoxazolamine paralysis times. Piperonyl butoxide pretreatment lengthened hexobarbitone sleeping times, but had no effect on zoxazolamine paralysis times. Warfarin survival was unaltered by pretreatment with either phenobarbital or piperonyl butoxide.
D000818:Animals; D005260:Female; D006591:Hexobarbital / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D010243:Paralysis / Q000139:chemically induced / Q000378:metabolism; D012737:Sex Factors; D012890:Sleep / Q000187:drug effects; D013045:Species Specificity; D014859:Warfarin / Q000494:pharmacology*; D015049:Zoxazolamine / Q000494:pharmacology*
D014859:Warfarin; D015049:Zoxazolamine; D006591:Hexobarbital