Pharmaceutical strategies in the treatment of obesity include drugs that regulate food intake, thermogenesis, fat absorption or fat metabolism. Fenproporex is the second most commonly consumed amphetamine-based anorectic worldwide. Besides, fenproporex is rapidly converted in vivo into amphetamine. Studies suggest that amphetamine induce neurotoxicity through generation of free radicals and mitochondrial apoptotic pathways by cytochrome c release, accompanied by a decrease of mitochondrial membrane potential. In the present work, we evaluated the locomotor activity and mitochondrial respiratory chain complexes activities in the brain of rats submitted to acute administration of fenproporex and amphetamine. Adult rats received a single injection of fenproporex (6,25; 12,5 or 25 mg/kg, intraperitoneal), amphetamine (2 mg/kg, intraperitoneal) or saline. Locomotor activity was measured 2 h after the injection. Mitochondrial respiratory chain enzymes activities were measured in the prefrontal cortex, hippocampus and striatum. Our results showed that amphetamine and fenproporex increased locomotor activity. Moreover, complexes I, II, III and IV were inhibited in prefrontal cortex and hippocampus by 6,25; 12,5 and 25 mg/kg of fenproporex. On the other hand, these activities were not affected in striatum. In addition, amphetamine inhibited complexes I, II, III and IV activity in prefrontal, hippocampus and striatum. The present findings suggest that acute exposure to fenproporex and AMPH alters locomotor activity and causes mitochondrial dysfunction.