title: Tc and Re chelates of 8alpha-amino-6-methyl-ergoline: synthesis and affinity to the dopamine D2 receptor.
abstract: 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 mercaptoacetylation 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=3-50 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.
authors.affiliation: Forschungszentrum Rossendorf e.V., Institut für Bioanorganische und Radiopharmazeutische Chemie, D-01314 Dresden, Germany. spies@fz-rossendorf.de
authors.forename: H
authors.initials: H
authors.lastname: Spies
authors.forename: B
authors.initials: B
authors.lastname: Noll
authors.forename: St
authors.initials: S
authors.lastname: Noll
authors.forename: M
authors.initials: M
authors.lastname: Findeisen
authors.forename: P
authors.initials: P
authors.lastname: Brust
authors.forename: R
authors.initials: R
authors.lastname: Syhre
authors.forename: R
authors.initials: R
authors.lastname: Berger
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D002614:Chelating Agents / Q000737:chemistry*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002851:Chromatography, High Pressure Liquid; D003001:Cloning, Molecular; D018491:Dopamine Agonists / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D004873:Ergolines / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D007202:Indicators and Reagents; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism*; D012211:Rhenium / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013667:Technetium / Q000737:chemistry*; D014018:Tissue Distribution
chemical_list: D002614:Chelating Agents; D018491:Dopamine Agonists; D004873:Ergolines; D007202:Indicators and Reagents; D017448:Receptors, Dopamine D2; D012211:Rhenium; D013667:Technetium