Abstract
Twenty-four hour LD50 values of secobarbital, pentobarbital, phenobarbital, in male Swiss-Webster mice weighing approximately 30 g each. The animals were adapted for three weeks in an environmental room equipped with an automatically-timed photoperiod lasting from 0800 to 2000 h daily. Each mouse was injected intraperitoneally at 6 h time intervals with either phenobarbital or chloral hydrate for toxicity analysis. Secobarbital, pentobarbital and hexobarbital were injected at 3 h time intervals. Peak toxicity was reached at D-0600 with all drugs screened except chloral hydrate which was 180 degrees out of phase. The drugs were least toxic at 1200 h with the exception of chloral hydrate which was least toxic at D-0600 h. These results suggest circadian periodicity in the toxicity of sedative hypnotics. Factors that could be responsible for these variations are discussed.
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References
Bianchine, J., Ferguson, F.: Acute Toxicity and lethal brain concentration of pentobarbital in young and adult albino rats. Proc. Soc. Exp. Biol. Med. 124, 1077–1079 (1967)
Butler, T. C.: Reduction and oxidation of chloral hydrate by isolated tissues in vitro. J. Pharmacol. Exp. Ther. 95, 360–362 (1949)
Cooper, J. R., Brodie, B. B.: The Enzymatic Metabolism of Hexobarbital. J. Pharmacol. Exp. Ther. 114, 409–417 (1955)
Cooper, J. R., Friedman, P. J.: The enzymic oxidation of chloral hydrate to trichloroacetic acid. Biochem. Pharmacol. 1, 76–82 (1958)
Davis, W.: Day-night periodicity in pentobarbital response of mice and the influence of socio-psychological conditions. Experientia 18, 235–236 (1962)
Deguchi, T.: Circadian rhythms of enzyme and running activity under ultradian lighting schedule. Am. J. Physiol. 232, E375-E381 (1977)
Friedman, A. H., Walker, C. A.: Circadian rhythms in rat midbrain and caudate nucleus biogenic amine levels. J. Physiol. (Lond.) 197, 77–85 (1968)
Friedman, A. H., Walker, C. A.: Rat brain amines, blood histamine and glucose levels in relation to circadian changes in sleep induced by pentobarbitone sodium. J. Physiol. 202, 133–146 (1969)
Friedman, P. J., Cooper, J. R.: The role of alcohol dehydrogenase in the metabolism of chloral hydrate. J. Pharmacol. Exp. Ther. 129, 373–376 (1960)
Holcslaw, T. L., Miya, T. S., Bousquet, W. S.: Circadian Rhythms in Drug Action and Drug Metabolism in the Mouse. J. Pharmacol. Exp. Ther. 195, 320–332 (1975)
Joannides, C., Parks, D.: Mechanism of Induction of hepatic microsomal drug metabolizing enzymes by a series of barbiturates. J. Pharm. Pharmacol. 27, 739–746 (1975)
Jori, A., Bianchetti, A., Prestini, P.: Relations between barbiturate brain levels and sleeping time in various experimental conditions. Biochem. Pharmacol. 19, 2687–2694 (1970)
Litchfield, J. T., Wilcoxon, F.: A Simplified Method of Evaluating Dose-Effect Experiments. J. Pharmacol. Exp. Ther. 96, 99–113 (1949)
Marshall, E. K., Owens, A. H.: Absorption, excretion and metabolic fate of chloral hydrate and trichloroethanol. Bull. Johns Hopkins Hosp. 95, 1–18 (1954)
Marte, E., Halberg, F.: Circadian susceptibility rhythm of mice to librium. Fed. Proc. 20, 305 (1961)
Muller, O.: Circadian rhythmicity in response to barbiturates. Naunyn-Schmiedebergs Arch. Pharmak. 270, 99 (1971)
Nair, V., Casper, R.: The Influence of light on daily rhythm in hepatic drug metabolizing enzymes in rat. Life Sci. 8, 1291–1298 (1969)
Nelson, W., Halberg, F.: An Evaluation of Time-Dependent Changes in Susceptibility of Mice to Pentobarbital Injection. Neuropharmacol. 12, 509–524 (1973)
Owens, A. H., Marshall, E. K., Broun, G. O., Zubrod, C. G., Lasagna, L.: A comparative evaluation of the hypnotic potency of chloral hydrate and trichloroethanol. Bull. Johns Hopkins Hosp. 96, 71–83 (1955)
Pauly, J., Scheving, L.: Temporal variations in the susceptibility of white rats to pentobarbital sodium and tremorine. Int. J. Neuropharmacol. 3, 651–658 (1964)
Radzialowski, F., Bousquet, W.: Daily rhythmic variations in hepatic drug metabolism in the rat and mouse. J. Pharmac. Exp. Ther. 163, 229–238 (1968)
Scheving, L., Vedral, D., Pauly, J.: A Circadian susceptibility rhythm in rats to pentobarbital sodium. Anat. Rec. 160, 741–750 (1968)
Vesell, E. S.: Genetic and Environmental Factors Affecting Hexobarbital Induced Sleeping Time (ST) in Mice. Fed. Proc. 27, 349 (1968)
Walker, C. A.: Twenty-four LD50 Rhythms in dl-amphetamines in Isolated and Aggregated Mice. Exp. Pharmacol. 1, 247–253 (1974)
Walker, C. A., Owasoyo, J. O.: The Influence of Serotonin, GABA and dl-dopa and the Circadian Rhythm in the Toxicity of Picrotoxin, Pentylenetetrazol and Phenobarbital in Mice. Int. J. Chronobiol. 2, 125–130 (1974)
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Sermons, A.L., Ross, F.H. & Walker, C.A. Twenty-four hour toxicity rhythms of sedative-hypnotic drugs in mice. Arch. Toxicol. 45, 9–14 (1980). https://doi.org/10.1007/BF00303289
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DOI: https://doi.org/10.1007/BF00303289