(Solved): part (c) [35 Marks] Structure A shows a tropane derivative TRODAT-1 that does not perieuar ...e bloo ...

part (c) [35 Marks] Structure A shows a tropane derivative TRODAT-1 that does not perieuar ...e bloodbrain barrier (BBB), while Structure

shows the radiopharmaceutical [99mTc]TRODAT-1, which is capable of crossing the BBB and binding the dopamine transporter. Excerpt taken from the Journal of Nuclear Medicine: "The dopamine transporter (DAT) protein, located on presynaptic dopamine neuron terminals, is involved in the regulation of dopamine levels. The striatum is a dopamine-rich region of the brain, is a critical component of motor and reward systems, and consequently has high densities of presynaptic DATs. Arising from its role in dopamine regulation, the DAT protein is a targeted binding site for various psychoactive drugs, imaging have shown excellent (e.g. cocaine) and amphetamines. Agentake sites in vivo and in vitro, especially for specific uptake in the dopamine reuptak is characterised by a selective loss of patients with Parks." i. Give reasons why the ligand in Structure

cannot penetrate the BBB while dopamine neurons. [99mTC]TRODAT-1 shown in Structure B can. iii. Using Structur diagnostic mode of action of

TRODAT-1. [End of Question 3]