Metabolism, distribution and anticonvulsant properties of N,N'- dimethoxymethyl-phenobarbital in the rat.
The in vivo metabolism of N,N'-dimethoxymethyl phenobarbital (DMMP) and the anticonvulsant properties of its metabolites were studied in the rat. At 10 and 30 minutes after i.p. administration, DMMP (ethyl-1-14C) represented less than 3% of plasma radioactivity, whereas N-monomethoxymethyl phenobarbital (MMP) was 78 and 75%, respectively, phenobarbital (PB) 12 and 20%, apparent mephobarbital 6 and 2% and less than 5% of the radioactivity remained at the origin. Peak levels of MMP were reached at 30 minutes in liver and 60 minutes in plasma and brain. At 4 hours, MMP had declined to 7% in plasma and was not detected in brain while PB rose to 93% of total 14C in plasma and brain. SKF-525A blocked (90%) the in vivo conversion of DMMP to MMP and completely inhibited the formation of PB, apparent mephobarbital and unidentified polar metabolites. MMP after oral administration was effective against maximum electroshock seizures at a time when brain levels of PB derived from MMP were insufficient to account for the total observed protection. However, MMP appears less potent than PB against pentylenetetrazol seizures.
D000818:Animals; D000927:Anticonvulsants / Q000378:metabolism* / Q000627:therapeutic use; D001921:Brain / Q000378:metabolism; D002855:Chromatography, Thin Layer; D004597:Electroshock; D008099:Liver / Q000378:metabolism; D008297:Male; D010433:Pentylenetetrazole; D010634:Phenobarbital / Q000031:analogs & derivatives* / Q000378:metabolism / Q000627:therapeutic use; D051381:Rats; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control; D013997:Time Factors
D000927:Anticonvulsants; D010433:Pentylenetetrazole; D010634:Phenobarbital