Cocaine increases the stimulation of dopamine release, at variance with atypical dopamine uptake inhibitors. New clues for the abuse liability of psychostimulants?

Dopamine uptake inhibitors (DUIs), such as cocaine and methylphenidate, are characterized by their ability to bind to the dopamine transporter (DAT) and prevent dopamine (DA) from being transported from the extracellular to the intracellular side of a neuronal terminal. It was originally posited that all DUIs would have the same effect on behavior, neurochemistry, and abuse liability in animal models as well as humans. However, a subset of these drugs, atypical DUIs (e.g. JHW007), have shown dissimilar profiles. While these DUIs have the same target and similar binding affinities to typical DUIs, their effects on behavior and neurochemistry are markedly different and predict little to no abuse liability in animal models.

多巴胺摄取抑制剂（DUIs），如可卡因和哌甲酯，其特征在于它们能够与多巴胺转运体（DAT）结合，并阻止多巴胺（DA）从神经元末梢的细胞外转运到细胞内。最初认为所有的多巴胺摄取抑制剂在动物模型以及人类中对行为、神经化学和滥用倾向都会产生相同的影响。然而，这些药物中的一部分，非典型多巴胺摄取抑制剂（例如JHW007），表现出不同的特性。虽然这些多巴胺摄取抑制剂与典型的多巴胺摄取抑制剂具有相同的靶点和相似的结合亲和力，但它们对行为和神经化学的影响明显不同，并且在动物模型中预测几乎没有滥用倾向。