Prolongation of barbiturate-induced sleeping time in mice by dimethylformamide (DMF) and other non-polar solvents: absence of an effect on hepatic barbiturate-metabolising enzymes.
Prior administration of non-polar solvents was shown to prolong sleeping time in female mice induced with pentobarbitone sodium (37.5 mg/kg). The doses of solvents to double sleeping time were extrapolated from individual dose-response curves: they were (g/kg i.p.): dimethylformamide (DMF) 1.15: polyethyleneglycol 2.0: glycerol 0.66: dimethylsulphoxide 1.78: and sulpholone 1.26. The prolongation of sleeping time with DMF was not due to inhibition of hepatic microsomal enzymes because mice pretreated with SK & F 525A (40 mg/kg i.p.) did not exhibit a much greater solvent-induced effect than occurred in control (unpretreated) mice. DMF prolonged sleeping time in mice injected with thiopentone sodium (37.5 mg/kg i.v.), a drug known not to have its duration of narcotic effect determined by microsomal enzyme metabolism. It is concluded that prolongation of barbiturate-induced sleeping time in mice by DMF is not due to an inhibitory effect of the solvent on the hepatic microsomal enzymes.
D000818:Animals; D001463:Barbiturates / Q000378:metabolism* / Q000494:pharmacology; D004126:Dimethylformamide / Q000494:pharmacology*; D004357:Drug Synergism; D005260:Female; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D051379:Mice; D011335:Proadifen / Q000494:pharmacology; D012890:Sleep / Q000187:drug effects; D013874:Thiopental / Q000494:pharmacology; D013997:Time Factors
D001463:Barbiturates; D004126:Dimethylformamide; D011335:Proadifen; D013874:Thiopental