https://doi.org/10.25772/AR93-7024
2012
Thesis
Master of Science
Pharmaceutical Sciences
Richard A Glennon
The dopamine transporter (DAT) mediates reuptake of dopamine from the synaptic cleft into the presynaptic terminus and plays a critical role in maintaining the normal function of dopaminergic neurons. DAT is the major target of widely abused psychostimulant drugs, including cocaine and amphetamine. DAT also figures into disease states, and it is a target for therapeutic drugs. It is known that cathinone and methcathinone, β-keto analogs of amphetamine and methamphetamine, respectively, produce pharmacological actions similar to amphetamine. Cathinone and methcathinone analogs are recently gaining in popularity on the clandestine market (e.g. ‘bath salts’). Cathinone and methcathinone analogs as well as their amphetamine and methamphetamine counterparts were synthesized and examined at the hDAT expressed in Xenopus oocytes. One of the two major constituents of ‘bath salts’ (i.e., mephedrone) produced an electrophysiological signature similar to the dopamine releasing agent S(+)-amphetamine while the other major constituent (i.e., MDPV) produced an electrophysiological signature similar to the dopamine re-uptake inhibitor cocaine.
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