Disease relevance of N-Methylphenobarbital

• Ependymoblastoma associated with prenatal exposure to diphenylhydantoin and methylphenobarbitone [1].
• A 38-yr-old woman who by history ingested 13 g methylphenobarbital, alcohol, and 6 g acetaminophen became comatose slowly over 4 d [2].
• In order to find a drug for the prevention of metabolic hyperbilirubinemia of the newborn, which has less sedative effects than phenobarbital (PB) the effect of methylphenobarbital (MPB) on the plasma bilirubin concentration of newborns was studied in a double blind trial [3].
• She was initially admitted following reports of several unusual episodes of syncope accompanied by convulsive movements and was discharged on mephobarbital with a diagnosis of atypical seizure disorder [4].

High impact information on N-Methylphenobarbital

• The interaction between Bm3R1 repressor and its operator, in vitro, was strongly inhibited by the addition of 2 mM pentobarbital or 2 mM methohexital (strong in vivo inducers of P450BM-3) but not by the same concentration of phenobarbital (a relatively weak inducer) or by mephobarbital (a non-inducer) [5].
• The influence of age and gender on the stereoselective metabolism and pharmacokinetics of mephobarbital in humans [6].
• These substantial influences of age and gender on the stereoselective disposition of mephobarbital are consistent with recent findings concerning the expression and regulation of cytochrome P450 enzymes [6].
• When mephenytoin was taken in the presence of mephobarbital, peak levels and AUC of S-mephenytoin increased while those of the R-enantiomer remained unchanged [7].
• Mephobarbital interferes with the analysis because methylation yields the same product as methylated phenobarbital [8].

Biological context of N-Methylphenobarbital

• Pharmacokinetics and bioavailability of methylphenobarbital in man [9].
• Effect of racemic mephobarbital and d-mephobarbital on hepatic microsomal enzyme induction in rat and monkey [10].
• Role of CYP2C19 in stereoselective hydroxylation of mephobarbital by human liver microsomes [11].
• The enantioselective protein binding of mephobarbital (MPB) was investigated in human plasma and human serum albumin solutions by equilibrium dialysis [12].
• Women have been shown to have a slower metabolism of mephobarbital and propranolol but an increased biotransformation of methylprednisolone, all three of which are metabolized by enzymes of the cytochrome P450 system [13].

Anatomical context of N-Methylphenobarbital

• The 4-hydroxylation of mephobarbital enantiomers was investigated by using human liver microsomes from the extensive metabolizers (EM) and poor metabolizers of CYP2C19 [11].
• The N-demethylation of N,N'-dimethylphenobarbital is an excellent model reaction to study in isolated hepatocytes because the primary metabolite, N-methylphenobarbital, is not further metabolized to an appreciable extent [14].
• They were used to compare the apparent permeability coefficient (Papp) of a series of lipophilic drugs, which should be affected by the mucus-layer, namely barbiturates (barbituric acid, barbital, phenobarbital, methylphenobarbital and heptabarbital) and testosterone, as a reference, to mucus-free Caco-2 cells [15].
• Effects of barbiturates (phenobarbital, mephobarbital, pentobarbital, hexobarbital and amobarbital) on the tonic and phasic responses of forelimbs were studied in the rats in which rigidity was induced by means of anemic decerebration [16].

Associations of N-Methylphenobarbital with other chemical compounds

• Estimates for the heat of adsorption ranged from -62.3 kJ/mol for barbituric acid to -91.1 kJ/mol for mephobarbital on the hydroxylated surface [17].
• Treatment of hepatocytes cultured on matrigel with 1 mM barbital, N-methylbarbital, cyclobarbital, hexobarbital, phenobarbital (PB), or mephobarbital (N-methyl-PB) resulted in increased amounts of CYP2B1/2 and CYP2C6 forms [18].

Gene context of N-Methylphenobarbital

• We sequenced all nine exons and exon-intron junctions of the cytochrome P450 2C19 (CYP2C19) gene from a Japanese subject with a lowered capacity of CYP2C19-mediated 4'-hydroxylation after an oral administration of mephobarbital [19].

Analytical, diagnostic and therapeutic context of N-Methylphenobarbital

• Urinary output of phenobarbital and the p-hydroxy derivatives of both mephobarbital and phenobarbital was measured by high pressure liquid chromatography [9].
• When supportive patient management fails to produce a satisfactory clinical course in a methylphenobarbital-intoxicated patient, hemoperfusion could be a useful adjunct to therapy [2].

References