The National Centre for Research and Development



CORE; Programme area: health; ID: 198887



Project title: EXtention of academia-based PLATFORM to antidepressant hits discovery


Acronym: PLATFORMex


Project Promoter: Institute of Pharmacology Polish Academy of Sciences


Polish partners: National Medicines Institute


Norwegian Partners: University of Tromsø The Arcitc University of Norway, Faculty of Health Science, Department of Medical Biology


Project cost (EUR): 935 426


Grant amount (EUR): 935 426

Duration: 30 months






Project summary:

Depression is among the top disorders reaching epidemic proportions in all countries. Available pharmacotherapy is based on drugs discovered over 50 years ago (all acted via monoaminergic systems in the brain) which have serious side effect profile and also only limited efficacy as the majority of depressed patients show partial or full resistance to these drugs. Thus, it is important to search for the new antidepressants overcoming limitations of current therapeutics what can be achieved also by targeting different groups of receptors including those from non-monoamine systems. Following the above, the Academia-based Platform was created to discover substances acting on serotonergic or glutamatergic systems as potential new antidepressant or anxiolytic drugs which was supported by the grant PNRF-103-AI-1/07 from Norway within the Polish-Norwegian Research Fund.The current Project aims at further development of the Platform research, based on the results obtained so far and also extending its scope on non-aminergic targets for antidepressant drug action. Based on lead compounds obtained in previous Project we plan to develop new series of compounds of hybrid structures combining pharmacophore elements of two or more 5-HT targets, i.e. SERT inhibitors and 5-HT1A postsynaptic agonist, and/or antagonist of 5-HT6 and 5-HT7 receptors. We will go further also with development of new glutamatergic agents by concentration our efforts on searching new mGlu7R allosteric modulators.
The most innovative but also challenging topics are focused on searching allosteric modulators of serotonin transporters and GABAB receptors which substantially extend the Platform research capabilities. Therapeutic potential of new compounds will be evaluated in commonly used behavioral models of depression. Finally, in order to ensure efficient designing or identification (in virtual screening) of active hits, further development of molecular modeling tools and methods will be continued.


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