RT Journal Article SR Electronic T1 Enzymatic N-methylation of phenelzine catalyzed by methyltransferases from adrenal and other tissues. JF Drug Metabolism and Disposition JO Drug Metab Dispos FD American Society for Pharmacology and Experimental Therapeutics SP 830 OP 834 VO 19 IS 4 A1 P H Yu A1 B A Davis A1 D A Durden YR 1991 UL http://dmd.aspetjournals.org/content/19/4/830.abstract AB Phenelzine (2-phenylethylhydrazine) was found to be methylated by enzymes obtained from bovine adrenal and some rat tissues in the presence of S-adenosylmethionine as methyl group donor. The methylated product was chromatographically (TLC and HPLC) identical with chemically synthesized N-methylphenelzine and the structure of this methylated phenelzine has been confirmed by a GC/MS procedure. Methylation occurs at the terminal nitrogen of phenelzine. The phenelzine methyltransferase in the bovine adrenal has a molecular weight and isoelectric point identical with that of bovine adrenal phenylethanolamine N-methyltransferase. The affinity of phenelzine for the methyltransferase is quite high, i.e. KM = 6.5 x 10(-5) M. Methylated phenelzine possesses much weaker inhibitory activity toward monoamine oxidase (MAO). It can, however, be deaminated by MAO to produce phenylacetaldehyde, and subsequently phenylacetic acid. We have also observed that other hydrazine compounds, such as hydralazine, can be methylated by the adrenal enzyme. Our finding of enzymatic methylation of hydrazine compounds is novel and it may play a role in the metabolism of hydrazine drugs.