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Comparison of the mGluR1 antagonist A-841720 in rat models of pain and cognition.
Morè, Lorenzo; Gravius, Andreas; Pietraszek, Malgorzata; Belozertseva, Irina; Malyshkin, Andrey; Shekunova, Elena; Barberi, Caroline; Schaefer, Daniela; Schmidt, Werner J; Danysz, Wojciech.
Afiliação
  • Morè L; Department of In-vivo Pharmacology, Merz Pharmaceuticals GmbH, Eckenheimer Landstrasse 100, Frankfurt am Main, Germany.
Behav Pharmacol ; 18(4): 273-81, 2007 Jul.
Article em En | MEDLINE | ID: mdl-17551319
In the current study we compared the potency of the selective metabotropic glutamate receptor (mGluR1) antagonist A-841720 (7-Azepan-1-yl-4-dimethylamino-7H-9-thia-1,5,7-triaza-fluoren-8-one) in rodent models of pain with its effects in models of learning and memory, to obtain information regarding the therapeutic window of this compound. A-841720 significantly reduced formalin-induced behaviours and complete Freund's adjuvant (CFA)-induced tactile allodynia, starting at doses of 1 and 10 mg/kg, respectively. At the dose of 3 mg/kg, however, A-841720 significantly reduced the percentage of spontaneous alternations in a radial-maze task. In contextual-fear conditioning, A-841720, given at the dose of 10 mg/kg before acquisition, significantly reduced freezing behaviour tested 24 h later. In the same task, repeated treatment for 5 days did not reduce the impairing effect of the challenge dose, indicating a lack of tolerance development. In a passive-avoidance task, A-841720 at 10 mg/kg administered before acquisition, significantly reduced the latency to enter the dark box on the retention test. Given that complete Freund's adjuvant is a better measure of analgesia, these results indicate that the selective mGluR1 antagonist A-841720 has analgesic potential in a dose range at which it also produces memory impairments. This diminishes its therapeutic potential for the treatment of chronic pain.
Assuntos
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Dor / Comportamento Animal / Cognição / Receptores de Glutamato Metabotrópico / Compostos Heterocíclicos com 3 Anéis / Aprendizagem Limite: Animals Idioma: En Revista: Behav Pharmacol Assunto da revista: CIENCIAS DO COMPORTAMENTO / FARMACOLOGIA Ano de publicação: 2007 Tipo de documento: Article País de afiliação: Alemanha País de publicação: Reino Unido
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Dor / Comportamento Animal / Cognição / Receptores de Glutamato Metabotrópico / Compostos Heterocíclicos com 3 Anéis / Aprendizagem Limite: Animals Idioma: En Revista: Behav Pharmacol Assunto da revista: CIENCIAS DO COMPORTAMENTO / FARMACOLOGIA Ano de publicação: 2007 Tipo de documento: Article País de afiliação: Alemanha País de publicação: Reino Unido