Tricyclic drugs: potent mutagenicity of traces of a nitroarene formed in the reaction of opipramol with nitrite.

ABSTRACT

The tricyclic psychotropic drug opipramol (Insidon) reacts in vitro with sodium nitrite in acidic solution to form products including mutagens for Salmonella typhimurium TA98 and TA100. Two aspects are particularly noteworthy. The strong mutagenicity of the crude reaction mixture is almost exclusively due to a compound which is present only in trace quantities (less than 0.1%). This mutagen was identified as a nitroarene, 4-[3-(2-nitro-9-(10H)-acridinon-10-yl)propyl]-1-piperazine-ethanol . Hence, while the formation of carcinogenic N-nitroso compounds from the interaction of nitrogen-containing compounds with nitrite is well known, the present study demonstrates the formation of a highly mutagenic C-nitro compound in the presence of nitrite.