Structure-Activity Relationships of Dopamine Transporter Pharmacological Chaperones.
Frontiers in cellular neuroscience January 1, 2022 Charles Sutton, Erin Q Williams, Hoomam Homsi et al. 13 citations
Mutations in the dopamine transporter gene cause Dopamine Transporter Deficiency Syndrome (DTDS), a fatal infantile parkinsonism-dystonia with no current treatment. Pharmacological chaperones can rescue some disease-causing variants. This study examined structure-activity relationships for two known chaperones, bupropion and ibogaine. The isoquinuclidine substituent of ibogaine and its analogs is important for chaperone efficacy. For bupropion, the secondary amine group is essential. Additional analogs with varying chemical modifications showed variable chaperone efficacies, contributing to the design of improved dopamine transporter pharmacological chaperones.