The derivation of nitrosamines from some therapeutic amines in the human environment

Five therapeutic drugs which are secondary and tertiary amines were investigated by reaction mechanisms for the derivation of nitrosamines in the human environments. These drugs are chlorpromazine (tranquilizer), methadone (analgesic), chloroquine (antimalarial), primaquine (antimalarial), and phenacetin (analgesic). Phenacetin is an N-acetylated secondary amine; chloroquine and primaquine are secondary amines; methadone and chlorpromazine are tertiary amines; and chloroquine is also a tertiary amine. In the human environments of the gastrointestinal tract, stomach, and bladder which generate the nitrosating agent, the derivation of various nitrosamines from these drugs has been presented. Dimethyl nitrosamine has been derived from methadone and diethylnitrosamine has been generated from chlorpromazine and chloroquine, respectively. Chlorpromazine, methadone, chloroquine, primaquine, and phenacetin have also produced by reaction mechanisms various nitrosamines of hitherto unknown carcinogenicity. The dimethylnitrosamine and diethylnitrosamine derived from methadone, chlorpromazine, and chloroquine are of proven carcinogenicity in experimental animals and they therefore constitute a hazard to humans.