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Assessment of the effects of NS11394 and L-838417, α2/3 subunit-selective GABA(A) [corrected] receptor-positive allosteric modulators, in tests for pain, anxiety, memory and motor function.
Hofmann, Martine; Kordás, Krisztina Sz; Gravius, Andreas; Bölcskei, Kata; Parsons, Chris G; Dekundy, Andrzej; Danysz, Wojciech; Dézsi, László; Wittko-Schneider, Ina M; Sághy, Katalin; Gyertyán, István; Horváth, Csilla.
Afiliação
  • Hofmann M; Departments of In vivo Pharmacology, Merz Pharmaceuticals GmbH, Frankfurt am Main, Germany.
Behav Pharmacol ; 23(8): 790-801, 2012 Dec.
Article em En | MEDLINE | ID: mdl-23075708
ABSTRACT
The aim of the present paper was to study the effects of GABAA receptor-positive modulators (L-838417 and NS11394) showing a preference for α2/3 subunits of the GABAA receptor, in models of pain, anxiety, learning, memory and motor function. These compounds have been suggested to have a favourable therapeutic profile over nonselective compounds such as diazepam. In this study, we tested both compounds for their effects in rat models of formalin-induced pain, spinal nerve-ligation-induced mechanical allodynia, plus maze, open field, rotarod, balance beam walking, contextual fear conditioning and Morris water maze. Both compounds exerted analgesic, but no anxiolytic effects. However, they induced motor side-effects, and learning and memory impairment at similar doses. Therefore, the anxiolytic effect and the lack of side-effects of these compounds, as described in the literature, could not be confirmed in the present study.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Triazóis / Benzimidazóis / Receptores de GABA-A / Agonistas de Receptores de GABA-A / Fluorbenzenos Idioma: En Ano de publicação: 2012 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Triazóis / Benzimidazóis / Receptores de GABA-A / Agonistas de Receptores de GABA-A / Fluorbenzenos Idioma: En Ano de publicação: 2012 Tipo de documento: Article