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Antiseizure activity of novel gamma-aminobutyric acid (A) receptor subtype-selective benzodiazepine analogues in mice and rat models.
Rivas, Felix M; Stables, James P; Murphree, Lauren; Edwankar, Rahul V; Edwankar, Chitra R; Huang, Shengming; Jain, Hiteshkumar D; Zhou, Hao; Majumder, Samarpan; Sankar, Subramanian; Roth, Bryan L; Ramerstorfer, Joachim; Furtmüller, Roman; Sieghart, Werner; Cook, James M.
Afiliación
  • Rivas FM; Department of Chemistry and Biochemistry, University of WisconsinsMilwaukee, Milwaukee, Wisconsin 53211, USA.
J Med Chem ; 52(7): 1795-8, 2009 Apr 09.
Article en En | MEDLINE | ID: mdl-19275170
The antiseizure activity of benzodiazepines (BDZs) 1-5 in mice and rats as animal models is described. These BDZs have selective efficacy for alpha2beta3gamma2 and alpha3beta3gamma2 GABA(A)-receptors. Significant anticonvulsant activity with little or no motor impairment and therapeutic indexes (TI) of 2.8-44 (mice, ip) were observed for compounds 2-4 in the subcutaneous metrazole seizure (scMET) test. In rats, orally (po) the TI was >5 to 105. These compounds represent novel leads in the search for anticonvulsants devoid of sedative, ataxic, and amnestic side effects.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Benzodiazepinas / Receptores de GABA-A / Anticonvulsivantes Límite: Animals Idioma: En Revista: J Med Chem Asunto de la revista: QUIMICA Año: 2009 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Benzodiazepinas / Receptores de GABA-A / Anticonvulsivantes Límite: Animals Idioma: En Revista: J Med Chem Asunto de la revista: QUIMICA Año: 2009 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos