Effects of Synthetic Cathinones on Brain Neurotransmitters

Abstract

Synthetic cathinones are the β-keto analogs of amphetamines and synthetic derivatives of cathinone naturally present in the khat plant (Catha edulis). There is very little data on pharmacology of cathinone derivatives. Like amphetamines, cathinones exert their stimulant effects via increasing synaptic concentrations of dopamine (DA), noradrenaline (NA), and serotonin (5-HT), albeit at various potencies. These compounds interact with plasma membrane transporters for DA, NA, and 5-HT. Some designer cathinones target monoamine transporters like substrates, such as amphetamine, while others are their blockers, like cocaine. Substrates, but not blockers, stimulate non-exocytotic release of neurotransmitters by reversing the normal direction of the transporter flux. Blockers of transport proteins are capable of increasing the extracellular level of neurotransmitters by preventing their reuptake after release from monoaminergic neurons. This chapter provides an overview of effects of synthetic cathinones on brain neurotransmitter levels. In vivo microdialysis studies demonstrated that administration of cathinones produced a potent and dose-dependent increase in the extracellular DA and 5-HT levels in the rat nucleus accumbens, frontal cortex, and striatum. It appears that certain synthetic cathinones potently affect extracellular levels of brain monoaminergic neurotransmitters, which may contribute to psychostimulatory, entactogenic, and hallucinogenic effect of these drugs and brings about the risk of addiction.