ALLOSTERIC POSITIVE EFFECTS OF PHENOLIC COMPOUNDS ON GABAA RECEPTOR IN PRIMARY NEURONAL CULTURES

GABRIELA N. REINER; SARA SANCHEZ REDONDO; CRISTINA SUÑOL; DANIEL A. GARCÍA

Congreso; Segunda Reunion Conjunta de Neurociencias; 2010

Sociedad Argentina de Neurociencia

ALLOSTERIC POSITIVE EFFECTS OF PHENOLIC COMPOUNDS ON GABAA RECEPTOR IN PRIMARY NEURONAL CULTURES. G Reiner1, S Sánchez Redondo2, C Suñol2 y DA García1. 1Dept. Chemistry, FCEFyN. Universidad Nacional de Córdoba. Argentina. 2Dept. Neurochemistry and Neuropharmacology. Institut d’Investigacions Biomèdiques de Barcelona, CSIC-IDIBAPS, Spain. E-mail: gabrielareiner@gmail.com We have previously demonstrated that thymol, a phenolic compound, possesses an important positive activity as modulator of GABAA receptor and GABA agonist. According to its similar structural properties with propofol, we have developed a pharmacophore model of activity on GABAA receptor for both compounds and derivatives (García et al., Neuropharmacol. 2006, 50:25). In the present work, we analyzed other different phenolic derivatives -carvacrol, eugenol and chlorothymol- which would confirm and/or improve this model. The effects on the GABAA receptor were evaluated by their ability to modulate the 3H-flunitrazepam binding on primary cultures of cortical neurons. The results showed an increment in the ligand binding induced by carvacrol and eugenol (EC50: 248Carv and 846Eug μM), and an enhancement exerted by chlorothymol but only until approximately 100 μM. Higher concentrations of chlorothymol reduced the binding possibly by the prevalence of an eventual cytotoxic effect. Bicuculline, a GABA antagonist, inhibited the stimulation produced by all compounds. Thus, the obtained results would indicate a positive modulation of GABAA receptor performed by all assayed compounds. Finally, the following studies are being directed to evaluate their effects on the neuronal viability. Supported by FONCyT, SECyT-UNC, IBRO, FIS 061212.