Dopamine transporter imaging ligand

C - Chemistry – Metallurgy – 07 – D

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C07D 451/02 (2006.01) A61K 51/00 (2006.01) A61K 51/04 (2006.01)

Patent

CA 2305754

The 3.alpha. isomer of RTI-55, RTI-352, is an effective in vivo binding ligand that reflects greater selectivity for the dopamine transporter than is observed with RTI-55. In addition, there is also a more rapid achievement of apparent equilibrium in the striatal-to-cerebellar ratio (compared to RTI-55) as the ratio peaks at about 30 min and is maintained for about 20 min thereafter. Such apparent equilibrium is useful in developing an approach to measuring the number of dopamine transporters present in tissues. Moreover, these results indicate that the utilization of 3.alpha. isomers of a variety of 3.beta. (substituted phenyl) tropanes will result in greater selectivity for dopamine transporters and a more rapid of achievement of apparent equilibrium.

L'isomère 3.alpha. de RTI-55 et de RTI-352 est un ligand efficace en matière de fixation in vivo qui fait montre d'une plus grande sélectivité à l'égard du transporteur de la dopamine que celle observée concernant RTI-55. On note, de surcroît, une mise en place plus rapide de l'équilibre apparent du rapport striatal/cérébelleux (en comparaison de RTI-55), les crêtes de rapport survenant au bout de 30 minutes environ et se maintenant pendant environ 20 minutes. Cet équilibre apparent se révèle utile dans la mise en place des modalités d'évaluation du nombre de transporteurs de la dopamine présents dans les tissus. Ces résultats indiquent, de surcroît, que l'emploi d'isomères 3.alpha. d'une variété de tropanes 3.beta. (à substitution phényle) débouche sur un renforcement de la sélectivité à l'égard des transporteurs de la dopamine ainsi que sur une mise en place plus rapide de l'équilibre apparent.

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