Tc and Re chelates of 8alpha-amino-6-methyl-ergoline: synthesis and affinity to the dopamine D₂ receptor

The influence of structural changes at the 8alpha-amino position of 8alpha-amino-6-methyl-ergoline on the lipophilicity and affinity to the D₂ receptor was studied.8alpha-amino- 6-methyl-ergoline (1) was converted into the derivatives (2a-f) by mercaptoacylation of the amino group to make it possible to prepare the rhenium and technetium complexes (3, 4a,b). Binding tests on cloned human dopamine D₂ receptors show that the affinities of the coordination compounds (IC₅₀ values between 50 and 240 nM) are less than those of the derivatives 2a-f (IC₅₀= 3 to 50 nM) but more than those of the parent compound 1. Biodistribution studies of the Tc complexes 4a,b performed on Wistar rats show a slow blood clearance with substantial accumulation and retention in the liver and kidneys and low brain uptake.