Anxiogenic effect of a new bioactive derived of quinolones

LOPEZ RIVILLI MARISA JUANA; BIGNANTE ELENA ANAHI; YRANZO GLORIA; MOLINA VICTOR ALEJANDRO

Tandil, Buenos Aires, Argentina.

Congreso; XL Reunión anual de la asociación argentina de Farmacología Experimental; 2008

Sociedad Argentina de Farmacología Experimental SAFE

ABSTRACT The pharmacological properties of benzodiazepines are due to their GABAA receptor modulating property, consequently benzodiazepine binding site (BBS) is an interesting target for the development of novel drugs with potential effect on anxiety. Several types of compounds, such as the pyrazolo-quinolinones are known to bind to the BBS with high affinity, and show a continuous pharmacological activity as agonists, inverse agonist or antagonists. A serie of novel 2-aryl-2H-pyrazolo[4,3-c]quinolin-3-ones derivatives were synthetized. Multistep synthesis was carried out starting from bromoanilines and diethyl ethoxymethylenemalonate via Gould-Jacobs reaction, and the further treatment with the appropriate analog of phenilhydracine gave the pyrazolo-quinolinone nucleus. We evaluated the effect of one of these drugs on the anxiety-like behavior of Wistar adult male rats (250-300 g) in the Elevated Plus Maze (EPM), an experimental paradigm to monitor anxiety. Animals were injected and tested thirty minutes later in the EPM. We evaluated the following doses: 0.25, 0.5, 1 y 3 mg/kg, a significant anxiogenic effect was observed with 3 mg/kg, since there was a significant reduction in the percentage of time spent on open arms of the EPM. These results suggest a possible role of this drug as an inverse agonist of the BBS