Description: New 2alpha-tropane amides as potential PET ligands for the dopamine transporter

This title appears in the Scientific Report : 2007

New 2alpha-tropane amides as potential PET ligands for the dopamine transporter

Positron emission tomography (PET) imaging of dopamine transporter (DAT) density in the brain is a potentially valuable tool for studying the etiopathology of degenerative brain disorders. The present study evaluated five new potential competitive inhibitors of DAT as ligands for PET. The evaluation...

Personal Name(s):	Drewes, B.
	Sihver, W. / Willbold, S. / Olsson, R. A. / Coenen, H. H.
Contributing Institute:	Nuklearchemie; INB-4 Zentralabteilung für Chemische Analysen; ZCH
Published in:	Nuclear medicine and biology, 34 (2007) S. 531 - 539
Imprint:	Amsterdam [u.a.] Elsevier 2007
Physical Description:	531 - 539
DOI:	10.1016/j.nucmedbio.2007.04.007
PubMed ID:	17591553
Document Type:	Journal Article
Research Program:	Funktion und Dysfunktion des Nervensystems
Series Title:	Nuclear Medicine and Biology 34
Subject (ZB):	Animals Corpus Striatum: metabolism Corpus Striatum: radionuclide imaging Dopamine Plasma Membrane Transport Proteins: metabolism Feasibility Studies Ligands Metabolic Clearance Rate Positron-Emission Tomography: methods Radiopharmaceuticals: chemical synthesis Radiopharmaceuticals: diagnostic use Radiopharmaceuticals: pharmacokinetics Rats Rats, Wistar Swine Tissue Distribution Tropanes: chemical synthesis Tropanes: diagnostic use Tropanes: pharmacokinetics Dopamine Plasma Membrane Transport Proteins Radiopharmaceuticals Tropanes J DAT ligands PET cocaine derivatives 2 alpha,3 beta tropanes
	Publikationsportal JuSER

Please use the identifier: http://dx.doi.org/10.1016/j.nucmedbio.2007.04.007 in citations.

Positron emission tomography (PET) imaging of dopamine transporter (DAT) density in the brain is a potentially valuable tool for studying the etiopathology of degenerative brain disorders. The present study evaluated five new potential competitive inhibitors of DAT as ligands for PET. The evaluation of the new compounds measured their ability to compete with the binding of the reference ligand 2beta-carbomethoxy-3beta-(4-[(131)I]iodophenyl)tropane [(131)I]beta-CIT to striatal and cortical membranes from rat and pig brain. Four of the new compounds structurally related to cocaine were synthesized in their 2alpha,3beta configuration; the most potent one, 3beta-(4-iodo-phenyl)-8-methyl-8-aza-bicyclo[3.2.1]octane-2alpha-carboxylic acid (2-fluoro-ethyl)-amide, was synthesized also in the 2beta,3beta configuration. For comparative studies in rat brain and new evaluation in pig brain homogenate, the established compounds beta-CIT, FP-CIT, PE2I and FETT were also synthesized and evaluated. Contrary to expectation, the 2alpha,3beta and 2beta,3beta isomers of 3-(4-iodo-phenyl)-8-methyl-8-aza-bicyclo[3.2.1]octane-2-carboxylic acid (2-fluoro-ethyl)-amide showed the same affinity constant for rat striatum (K(i)=200 nM+/-34), but in pig striatum and rat and pig cortex the 2alpha,3beta form even had a higher affinity than the 2beta,3beta form.