Bioguided purification and pharmacological characterization of neuroactive compounds present in Aloysia virgata

CRISTINA WASOWSKI; MARIEL MARDER

Rosario, Argentina

Congreso; XLI Reunion Anual de la Sociedad Argentina de Farmacolog¨ªa Experimental (SAFE); 2009

Using the guide of a competitive assay for the benzodiazepine binding site (BDZ-bs) in the GABAA receptor two active diterpenes were isolated from the aerial parts of Aloysia virgata (Ru¨ªz & Pav¨®n). These compounds; identified as (16R)-16, 17, 18-trihydroxyphyllocladan-3-one (1) and (16R)-16, 17-dihydroxyphyllocladan-3-one (2) on the basis of spectral data; competitively inhibited the binding of [3H]-FNZ to the BDZ-bs with Ki ¡À SEM values of 56 ¡À 19 ¦ÌM and 111 ¡À 13 ¦ÌM, respectively. The behavioral actions of these diterpenes, i.p. administered in mice, were examined in the plus maze, hole board, locomotor activity and light/dark tests. Compound 1 exhibited anxiolytic-like effects in mice evidenced by a significant increase of the parameters measured in the hole board test (number of head dips at 0.3 mg/kg and 3 mg/kg, rears at 1 mg/kg and time spent head dipping at 3 mg/kg), in the plus maze assay (percentage of open arm entries at 1 mg/kg) and in the light/dark test (time in light and the number of transitions at 1 mg/kg). Compound 2 augmented the number of rearings in the hole board apparatus (at 0.3 and 1 mg/kg) and the locomotor activity (at 1 mg/kg). These results reveal the presence of neuroactive compounds in Aloysia virgata.