Conversion of dimethoxymethyl-diphenylbarbituric acid (DMMDPB) to diphenylbarbituric acid (DPB) in the rat

A. Raines, D. Flockhart, K. L. Dretchen, A. Singh, D. Thacker, A. Yacobi, D. Moros, B. H. Levitt, D. Abernethy

Research output: Contribution to journalArticlepeer-review


DPB exerts anticonvulsant properties in rodents in the maximal electroshock test and against seizures and death produced by pentylenetetrazole. As with phénobarbital (PB), but unlike most barbiturates, neurotoxic doses of DPB are readily separable from anticonvulsant doses but unlike PB, DPB lacks significant hypnotic properties. DMMDPB shares anticonvulsant properties with DPB in the rat. Studies were undertaken to determine whether DMMDPB is converted to DPB in vivo. Male rats weighing 250 G were given DMMDPB in a dose of 150 mg/kg by gavage suspended in PEG 400 in a total volume of 1 ml and a 0.5 ml wash. Blood was sampled every 30 minutes for up to 7 hours. An HPLC method utilizing a solid phase extraction was developed for detection of DMMDPB and DPB. The limit of quantification was 0.5 (μg/ml. Serum levels of the order of 2.5 to 4 ug/ml were observed 3 hours after dosing and were still rising; in the one animal sampled until 7 hours, levels were 7 μg/ml and still rising. At no time after DMMDPB dosing could DMMDPB be detected. These data show complete conversion of DMMDPB to DPB and are consistant with slow absorption followed by rapid and complete pre-systemic conversion to DPB.

Original languageEnglish (US)
Pages (from-to)A155
JournalFASEB Journal
Issue number3
StatePublished - 1996
Externally publishedYes

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics


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