INHIBITORY ACTIVITY OF NATURAL CICLIC KETONES ON THE GABAA RECEPTOR. CITOTOXICITY STUDIES.

SÁNCHEZ-BORZONE M.; GARCIA DA

Huerta Grande

Congreso; XXVIII Congreso de la Sociedad Argentina de Investigación en Neurociencias; 2013

Sociedad Argentina de Investigación en Neurociencias

The GABAA receptor is he main inhibitory receptor of the Central Nervous System. It possesses binding sites for drugs other than the neurotransmitter GABA, including benzodiazepines, barbiturates, and the convulsant picrotoxine which behave as allosteric modulators or channel blockers. The study of this last site is especially relevant since it constitutes the action site of widely used neurotoxic organochlorine pesticides. Considering the anticonvulsant activity of thujone, by blocking of chloride channel associated to GABAA receptor, in the present work we analyzed the effect of five cyclic ketones structurally similar, on the GABA stimulated increment of [3H]flunitrazepam binding. The assays were done by using primary cultures of cortical neurons. The results showed that not only thujone but also all the ketones included in this research, were able to reduce the GABA induced increment of the [3H]flunitrazepam binding. Taking into account the action mechanism associated to thujone on the receptor, we can suggest that the ketones studied would also recognize the picrotoxine site in the GABAA receptor. However, this last hypothesis should be confirmed by using specific ligands of that blocking site. All ketones did not affected neuronal viability and red cell integrity.