Anticonvulsant sulfamides with affinity for the GABAa receptor and anxiolytic activity in mice

WASOWSKI CRISTINA; GAVERNET LUCIANA; BARRIOS IVANA A.; BRUNO BLANCH LUIS E.; MARDER MARIEL

Rosario

Congreso; 41 Reunión anual de la Asociación Argentina de Farmacología Experimental; 2009

MES and PTZ tests with promising results, were tested for theiraffinity for the benzodiazepine binding site (BDZ-bs) in theGABAA receptor. The most active compounds found; N,N´-dicyclohexylsulfamide (1) and N,N´-diphenethylsulfamide (2),competitively inhibited the binding of [3H]-FNZ to the BDZ-bswith Ki ± SEM values of 27.7 ± 4.5 μM (n= 3) and 6.0 ± 1.2 μM(n= 3), respectively. The behavioral actions of these sulfamides,i.p. administered in mice, were examined in the plus maze, holeboard and locomotor activity. Compound 1 exhibited anxiolyticlikeeffects in mice evidenced by a significant increase of theparameters measured in the hole board test (at 0.3, 1 and 3 mg/kg)and the plus maze assay (at 1 mg/kg). Compound 2 evidencedanxiolytic activity in the plus maze test at 1 mg/kg. Locomotoractivity of mice was not modified by compound 1 or 2 at the dosestested. Anxiety represents a major problem for people withepilepsy. The use of these anticonvulsant sulfamides would bebeneficial to individuals who suffer from both disorders.