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

C. WASOWSKI; L. GAVERNET; I. A. BARRIOS; L. E. BRUNO-BLANCH; M. MARDER

Rosario, Argentina

Congreso; XLI Reunion Anual de la Sociedad Argentina de Farmacología Experimental; 2009

A set of sulfamates and sulfamides designed, synthesized and evaluated against MES and PTZ tests with promising results were tested for their affinity for the benzodiazepine binding site (BDZ-bs) in the GABAA receptor. The most active compounds found; N,NL-dicyclohexylsulfamide (1) and N,NL-diphenethylsulfamide (2), competitively inhibited the binding of [3H]-FNZ to the BDZ-bs with Ki } SEM values of 27.7 } 4.5 ƒÊM (n= 3) and 6.0 } 1.2 ƒÊM (n= 3), respectively. The behavioral actions of these sulfamides, i.p. administered in mice, were examined in the plus maze, hole board and locomotor activity assays. Compound 1 exhibited anxiolytic-like effects in mice evidenced by a significant increase of the parameters 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 evidenced anxiolytic activity in the plus maze test at 1 mg/kg. Locomotor activity of mice was not modified by compound 1 or 2 at the doses tested. Anxiety represents a major problem for people with epilepsy. The use of these anticonvulsant sulfamides would be beneficial to individuals who suffer from both disorders.