title: Inhibitors of indoleethylamine N-methyltransferase. Derivatives of 3-methyl-2-thiazolidinimine. In vitro, in vivo, and metabolic studies.
abstract: A variety of substituent groups has been attached to the exocyclic imine function of 2-imino-3-methylthiazolidine (1) in a search for metabolic precursors of this potent inhibitor of the enzyme indoleethylamine N-methyltransferase (INMT) which would exhibit superior pharmacodynamic properties in animals. It has been determined that chemically stable derivatives of 1 based on succinic, nicotinic, and N-acylated amino acids, although they lack in vitro efficacy, are potent inhibitors of INMT when administered orally or intravenously to rabbits. Metabolic studies carried out with 14C-labeled N,N'-bix(3-methyl-2-thiazolidinylidene)succinamide (3) have established that conversion of this compound to 1 occurs both in the whole rabbit and in the isolated rabbit liver. 1 itself has been shown to be metabolically inert in rabbits, being excreted primarily in the urine.
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001711:Biotransformation; D006801:Humans; D007097:Imines / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000201:enzymology; D008297:Male; D008780:Methyltransferases / Q000037:antagonists & inhibitors*; D011817:Rabbits; D013844:Thiazoles / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D014018:Tissue Distribution; D014363:Tryptamines / Q000037:antagonists & inhibitors
chemical_list: D007097:Imines; D013844:Thiazoles; D014363:Tryptamines; D008780:Methyltransferases; C021439:indoleethylamine N-methyltransferase