IFLYSIB   05383
INSTITUTO DE FISICA DE LIQUIDOS Y SISTEMAS BIOLOGICOS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
ANTICONVULSANT SULFAMIDES WITH AFFINITY FOR THE GABAA RECEPTOR AND ANXIOLYTIC
Autor/es:
WASOWSKI C.A, GAVERNET L.B, BARRIOS I.A.B, BRUNO-BLANCH L.E.B, MARDER M.A
Lugar:
Rosario, Argentina
Reunión:
Congreso; Cuadragésima primera REUNION ANUAL de SAFE; 2009
Resumen:
ANTICONVULSANT SULFAMIDES WITH AFFINITY FOR THE GABAA RECEPTOR AND ANXIOLYTIC ACTIVITY IN MICE.A RECEPTOR AND ANXIOLYTIC ACTIVITY IN MICE.. Wasowski C.a, Gavernet L.b, Barrios I.A.b, Bruno-Blanch L.E.b, Marder M.a a IQUIFIB (UBA-CONICET), Facultad de Farmacia y Bioquímica, Junín 956 (C1113AAD), Buenos Aires, Argentina.a, Gavernet L.b, Barrios I.A.b, Bruno-Blanch L.E.b, Marder M.a a IQUIFIB (UBA-CONICET), Facultad de Farmacia y Bioquímica, Junín 956 (C1113AAD), Buenos Aires, Argentina.IQUIFIB (UBA-CONICET), Facultad de Farmacia y Bioquímica, Junín 956 (C1113AAD), Buenos Aires, Argentina. b Química Medicinal, Departamento de Ciencias Biológicas, UNLP, calle 47 y 115 (B1900BJW), La Plata, Argentina.Química Medicinal, Departamento de Ciencias Biológicas, UNLP, calle 47 y 115 (B1900BJW), La Plata, Argentina. mmarder@qb.ffyb.uba.ar 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´-dicyclohexylsulfamide (1) and N,N´-diphenethylsulfamide (2), competitively inhibited the binding of [3H]-FNZ to the BDZ-bs with 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, 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.A 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-bs with 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, 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.N,N´-dicyclohexylsulfamide (1) and N,N´-diphenethylsulfamide (2), competitively inhibited the binding of [3H]-FNZ to the BDZ-bs with 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, 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.3H]-FNZ to the BDZ-bs with 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, 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.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.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.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.