PMID: 2509086Jan 1, 1989Paper

Chronotoxicity of sodium valproate and its mechanisms in mice: dose-concentration-response relationship

Chronobiology International
S OhdoN Ogawa

Abstract

A significant circadian rhythm of acute toxicity was demonstrated in mice with intraperitoneal (i.p.) injection of sodium valproate (VPA). The role of pharmacokinetics on the rhythms of the toxicity and electroshock seizure (ES) threshold was investigated. ICR male mice, housed under a light-dark (12:12) cycle, were injected intraperitoneally 1200 mg/kg for the acute toxicity study and 300 mg/kg for the anticonvulsant effect study. In the acute toxicity, the highest mortality was found when VPA was injected at 1700 and the lowest at 0900 or 0100. The time course of mean plasma and brain VPA concentrations after an injection of VPA was not different between mice injected at 1700 and mice injected at 0100. In the anticonvulsant effect, no significant circadian rhythm was demonstrated for both the ES threshold and the plasma VPA concentrations after i.p. injection, although a significant rhythm has been reported for them after oral administration. The results suggest that the circadian rhythm in the mortality after an i.p. injection of VPA may be due to the rhythm in the sensitivity of the central nervous system to the drug and that the mechanism underlying the rhythm of VPA acute toxicity is different from that of the anticonvuls...Continue Reading

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Citations

Sep 1, 1992·Journal of Clinical Pharmacology·S OhdoN Ogawa
Mar 5, 2013·Current Neurology and Neuroscience Reports·Sriram RamgopalTobias Loddenkemper
Jul 1, 1995·European Journal of Pharmacology·S OhdoJ G Song
Oct 6, 1995·European Journal of Pharmacology·S OhdoT Sugiyama
Mar 15, 2011·Journal of Clinical Neurophysiology : Official Publication of the American Electroencephalographic Society·Tobias LoddenkemperSanjeev V Kothare
Jan 4, 2003·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Shigehiro Ohdo
Mar 15, 2001·Chronobiology International·D M ReithD McLaughlin
Jun 24, 2020·Neuropharmacology·Isabel Vieira de Assis LimaAntônio Carlos Pinheiro de Oliveira

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