The effect of diazepam on brain levels of S-adenosyl-L-methionine and S-adenosyl-L-homocysteine: possible correlation with protection from methionine sulfoximine seizures.
Administration of the long latency convulsant, L-methionine-d,1-sulfoximine (MSO) results in an increase in brain methylation flux. We determined the effects of the anticonvulsant, diazepam (DZ) on MSO seizures and on brain levels of S-adenosyl-L-methionine (AdoMet) and S-adenosyl-L-homocysteine (AdoHcy) to indicate possible alterations in the brain methylation pathway. We report a dose related inhibition of MSO seizures by DZ. In addition, DZ significantly increased brain levels of AdoMet and AdoHcy and reversed the MSO-induced decreases in AdoMet and AdoHcy. DZ also blocked the MSO induced increase in the methylation index (AdoMet/AdoHcy). The data indicates an inhibition of MSO induced increases in brain methylation by DZ. Possible mechanisms for the effect of DZ on the cerebral methylation pathway are discussed.
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D003975:Diazepam / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006710:Homocysteine / Q000031:analogs & derivatives*; D008297:Male; D008717:Methionine Sulfoximine / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008745:Methylation; D051379:Mice; D011930:Reaction Time / Q000187:drug effects; D012435:S-Adenosylhomocysteine / Q000378:metabolism*; D012436:S-Adenosylmethionine / Q000378:metabolism*; D012640:Seizures / Q000139:chemically induced* / Q000378:metabolism
D006710:Homocysteine; D008717:Methionine Sulfoximine; D012436:S-Adenosylmethionine; D012435:S-Adenosylhomocysteine; D003975:Diazepam