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Novel competitive antagonists for P2 purinoceptors.
van Rhee, A M; van der Heijden, M P; Beukers, M W; IJzerman, A P; Soudijn, W; Nickel, P.
Afiliación
  • van Rhee AM; Center for Bio-Pharmaceutical Sciences, Division of Medicinal Chemistry, Leiden, The Netherlands.
Eur J Pharmacol ; 268(1): 1-7, 1994 Jun 15.
Article en En | MEDLINE | ID: mdl-7925607
Binding of the radioligand [35S]adenosine 5'-O-(2-thiodiphosphate) (ADP beta 35S) to P2 gamma purinoceptors on turkey erythrocyte membranes was used to determine the affinity of suramin and various suramin congeners belonging to different structure classes (large urea, small urea, dibenzamides and benzamides) for these receptors. Suramin was shown to be a competitive antagonist with a Ki value of 7.3 +/- 2.2 microM. The simple benzamide compound XAMR0721 (8-(3,5-dinitrophenylene carbonylimino)-1,3,5-naphthalene trisulfonate, trisodium salt) displays a high affinity for the P2 gamma purinoceptor (Ki value of 19 +/- 6 microM). Similar to suramin, compound XAMR0721 is a competitive antagonist at P2 gamma purinoceptors. In contrast to suramin, which is a potent inhibitor of the ecto-nucleotidase activity in human blood cells (44 +/- 2% residual activity at 100 microM), compound XAMR0721 is hardly active in this assay (93 +/- 1% residual activity at 100 microM). So XAMR0721, the first competitive antagonist for P2 purinoceptors that is able to discriminate between P2 purinoceptor affinity and ecto-nucleotidase activity, is an interesting pharmacological tool for the characterization of P2 purinoceptor mediated effects.
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Suramina / Antagonistas del Receptor Purinérgico P2 Límite: Animals / Humans Idioma: En Revista: Eur J Pharmacol Año: 1994 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Países Bajos
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Suramina / Antagonistas del Receptor Purinérgico P2 Límite: Animals / Humans Idioma: En Revista: Eur J Pharmacol Año: 1994 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Países Bajos