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Searching for lead molecules as potential new CNS agents in the serotonin 5-HT6 screening assay

Beata Duszyńska 1Andrzej J. Bojarski 1Jan Boksa 1Tomasz Lenda 1Dorota Kamińska 1Marcin Cybulski 2Łukasz S. Kaczmarek 2

1. Polish Academy of Sciences. Institute of Pharmacology, Smętna 12, Kraków 31-343, Poland
2. Pharmaceutical Research Institute (IF), Rydygiera 8, Warszawa 01-793, Poland

Among 14 different serotonin receptor subtypes 5-HT6 and 5-HT7 ones, simultaneously discovered in 1993, are classified as last members in 5-HT receptor superfamily. They both show high affinity for a wide range of agents used in psychiatry, and many drug discovery programs have been initiated, which were focused on the search of selective 5-HT6 and/or 5-HT7 ligands. In the filed of serotonergics we have successfully concentrated on the development of compounds active at 5-HT1A, 5-HT2A and 5-HT7 receptors and recently our studies were extend on 5-HT6 ligands. Strategy that was previously elaborated for investigations of 5-HT7 receptors was applied and both an in-house and external compounds libraries were screened in 5-HT6 receptor binding assay. Several lead molecules have been identified for further structure optimization on the basis of 5-HT6 receptor homology model.

This study was partly supported by the Network "Synthesis, structure and therapeutic properties of compounds and organic substances" coordinated by the Institute of Organic Chemistry Polish Academy of Sciences.


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Submitted: 2008-03-15 23:35
Revised:   2009-06-07 00:48