Identification of the benztropine analog [¹²⁵I]GA II 34 binding site on the human dopamine transporter.

ABSTRACT: The dopamine transporter (DAT) is a neuronal membrane protein that is responsible for reuptake of dopamine (DA) from the synapse and functions as a major determinant in control of DA neurotransmission. Cocaine and many psychostimulant drugs bind to DAT and block reuptake, inducing DA overflow that forms the neurochemical basis for euphoria and addiction. Paradoxically, however, some ligands such as benztropine (BZT) bind to DAT and inhibit reuptake but do not produce these effects, and it has been hypothesized that differential mechanisms of binding may stabilize specific transporter conformations that affect downstream neurochemical or behavioral outcomes. To investigate the binding mechanisms of BZT on DAT we used the photoaffinity BZT analog [¹²⁵I]N-[n-butyl-4-(4‴-azido-3‴-io

SUBMITTER: Tomlinson MJ 

PROVIDER: S-EPMC8295913 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature