Use of buccal micronucleus assay to determine mutagenicity induced by amfepramone in humans and the protective effects of vitamin C.

The abusive use of amfepramone in Brazilian population has grown in recent years. Few studies have been conducted on amphetamine with respect to DNA damage, and there have been no apparent investigations examining the influence of amfepramone on humans. The aim of this study was to determine the possible mutagenic actions of amfepramone on humans using the micronucleus (MN) assay with buccal cells and the effects of supplementation with vitamin C as a potential protective agent. The study included 108 females with 52 as control and 56 taking amfepramone at 120 mg/d for at least the whole previous month. All women were intentionally selected to be nonsmokers and nondrinkers. After 30 d of amfepramone women were given amfepramone plus vitamin C use at 1000 mg/d for another month. Results showed a marked increase in the number of MN in amfepramone users in both basal and differentiated cells, indicating a mutagenic action. After vitamin C supplementation, a significant decrease in the frequency of MN and apoptosis was observed. Evidence indicates that the main mechanism of action of amfepramone in inducing DNA damage occurs through formation of reactive oxygen species (ROS), intercalation and topoisomerase binding, attributed to the presence of an N-dialkyl group. In addition, data demonstrated that vitamin C effectively inhibited amfepramone-induced DNA damage.

DNA damage in brain cells and behavioral deficits in mice after treatment with high doses of amantadine.

Amantadine (AMA) is an uncompetitive antagonist of the N-methyl-d-aspartate receptor, with clinical application, acting on treatment of influenza A virus and Parkinson's disease. It has been proposed that AMA can indirectly modulate dopaminergic transmission. In high doses, the central nervous system is its primary site of toxicity. To examine deleterious effects on CNS induced by AMA, this study evaluated possible neurobehavioral alterations induced by AMA such as stereotyped behavior, the effects on locomotion and memory and its possible genotoxic/mutagenic activities. Adult male CF-1 mice were treated with a systemic injection of AMA (15, 30 or 60 mg kg(-1) ) 20 min before behavioral tasks on open field and inhibitory avoidance. Higher AMA doses increased the latency to step-down inhibitory avoidance test in the training session in the inhibitory avoidance task. At 60 mg kg(-1) AMA induced impairing effects on locomotion and exploration and hence impaired habituation to a novel environment. Stereotyped behavior after each administration in a 3-day trial was observed, suggesting effects on dopaminergic system. Amantadine was not able to induce chromosomal mutagenesis or toxicity on bone marrow, as evaluated by the micronucleus assay. At the lowest dose tested, AMA did not induce DNA damage and it was unable to impair memory, locomotion, exploration or motivation in mice. However, higher AMA doses increased DNA damage in brain tissue, produced locomotor disturbances severe enough to preclude testing for learning and memory effects, and induced stereotypy, suggesting neurotoxicity.