Abstract
Fenproporex is the second most commonly amphetamine-based anorectic consumed worldwide; this drug is rapidly converted into amphetamine, in vivo, and acts by increasing dopamine levels in the synaptic cleft. Considering that fenproporex effects on the central nervous system are still poorly known and that acetylcholinesterase is a regulatory enzyme which is involved in cholinergic synapses and may indirectly modulate the release of dopamine, the present study investigated the effects of acute administration of fenproporex on acetylcholinesterase activity in brain of young rats. Young male Wistar rats received a single injection of fenproporex (6.25, 12.5 or 25mg/kg i.p.) or vehicle (2% Tween 80). Two hours after the injection, the rats were killed by decapitation and the brain was removed for evaluation of acetylcholinesterase activity. Results showed that fenproporex administration increased acetylcholinesterase activity in the hippocampus and posterior cortex, whereas in the prefrontal cortex, striatum and cerebellum the enzyme activity was not altered. In conclusion, in the present study we demonstrated that acute administration of fenproporex exerts an effect in the cholinergic system causing an increase in the activity of acetylcholinesterase in a dose-dependent manner in the hippocampus and posterior cortex. Thus, we suggest that the imbalance in cholinergic homeostasis could be considered as an important pathophysiological mechanism underlying the brain damage observed in patients who use amphetamines such as fenproporex.
Highlights
Fenproporex is the second most commonly used anorectic substance in the world (Cohen 2009)
Fenproporex promotes the reduction of food intake, through a change in the chemical control of nerve impulse transmission; the drugs presents a similar effect to that of amphetamine, including central nervous system stimulation, which acts by blocking the reuptake of norepinephrine and dopamine, thereby increasing the levels of these neurotransmitters in the synaptic cleft (Coutts et al 1986)
Considering that fenproporex is rapidly converted in vivo into amphetamine leading to increased extracellular dopamine levels in brain and that AChE is an enzyme regulator involved in cholinergic transmission and can indirectly modulate dopamine release, the present study investigated the effects of acute administration of fenproporex on the enzyme activity of AChE in brain of young rats
Summary
Fenproporex is the second most commonly used anorectic substance in the world (Cohen 2009). Fenproporex promotes the reduction of food intake, through a change in the chemical control of nerve impulse transmission; the drugs presents a similar effect to that of amphetamine, including central nervous system stimulation, which acts by blocking the reuptake of norepinephrine and dopamine, thereby increasing the levels of these neurotransmitters in the synaptic cleft (Coutts et al 1986). Amphetamine compounds, including fenproporex, are classified as indirect-acting dopaminergic agents. These compounds have complex actions on the noradrenaline and dopamine presynaptic terminal, releasing or blocking neuronal reuptake of noradrenaline and dopamine. The end result of the actions of amphetamines in dopaminergic terminals is an increased concentration of dopamine in the synaptic cleft. The dopamine system is among the most important neurotransmitter systems and its relationship to the cholinergic system has been widely studied (Hefco et al 2004)
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