Search for new treatment approaches in schizophrenia: in vitro studies of potential N-methyltransferase inhibitors.

Partially purified rabbit lung N-methyltransferase (NMT) was used in an in vitro assay to screen various amines and substrate analogs as potential inhibitors, N-Methyltryptamine (NMeT, 10(-3 M) and 14C-S-adenosyl-L-methionine (14C-SAM, 2.5 X 10(-5) M) were used as substrates to form 14C-N, N-dimethyltryptamine (14C-DMT). By thin layer chromatography the product was identified as having the same Rf as authentic DMT. Of 129 compounds studied S-adenosyl-L-homocysteine (SAH), 2-(2-aminoethyl)-5,6-dichlorobenzimidazole dihydrochloride (SKF No62817-A2), DMT, an equimolar mixture of adenosine plus DL-homocysteine, N-(2-aminoethyl)-pyrrolidine, and 2-(2-aminoethyl)-pyridine showed definite inhibitory properties. These constitute potential lead compounds for further research.