Halogenation of a capsaicin analogue leads to novel vanilloid TRPV1 receptor antagonists. (Articolo in rivista)

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  • Halogenation of a capsaicin analogue leads to novel vanilloid TRPV1 receptor antagonists. (Articolo in rivista) (literal)
Anno
  • 2003-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1038/sj.bjp.0705387 (literal)
Alternative label
  • Appendino G, Harrison S, De Petrocellis L, Daddario N, Bianchi F, Schiano Moriello A, Trevisani M, Benvenuti F, Geppetti P, Di Marzo V. (2003)
    Halogenation of a capsaicin analogue leads to novel vanilloid TRPV1 receptor antagonists.
    in British journal of pharmacology; NATURE PUBLISHING GROUP,, LONDON (Regno Unito)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Appendino G, Harrison S, De Petrocellis L, Daddario N, Bianchi F, Schiano Moriello A, Trevisani M, Benvenuti F, Geppetti P, Di Marzo V. (literal)
Pagina inizio
  • 1417 (literal)
Pagina fine
  • 1424 (literal)
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  • 139 (literal)
Rivista
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  • Schiano Moriello A. assegnista ICB IF 2002: 3,45. Settore disciplinare Farmacologia (categorie ISI-CRUI). La rivista è nella fascia di eccellenza del settore (da 2,99 a 25,57). IF ricalcolato in base al rango: 0,867. ImmediacyIndex 0,59; Cit Half-Life 6,0. (literal)
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  • 8 (literal)
Note
  • ISI Web of Science (WOS) (literal)
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  • 1. Ist Cibernetica, Naples, Italy 2. DiSCAFF, I-28100 Novara, Italy 3. Univ Ferrara, Dipartimento Med Sperimentale & Clin, I-44100 Ferrara, Italy 4. CNR, Ist Chim Biomol, Endocannabinoid Res Grp, I-80078 Naples, Italy (literal)
Titolo
  • Halogenation of a capsaicin analogue leads to novel vanilloid TRPV1 receptor antagonists. (literal)
Abstract
  • The C-5 halogenation of the vanillyl moiety of resiniferatoxin, an ultrapotent agonist of vanilloid TRPV1 receptors, results in a potent antagonist for these receptors. Here, we have synthesized a series of halogenated derivatives of 'synthetic capsaicin' (nonanoyl vanillamide=nordihydrocapsaicin) differing for the nature (iodine, bromine-chlorine) and the regiochemistry (C-5, C-6) of the halogenation. 2. The activity of these compounds was investigated on recombinant human TRPV1 receptors overexpressed in HEK-293 cells. None of the six compounds exerted any significant agonist activity, as assessed by measuring their effect on TRPV1-mediated calcium mobilization. Instead, all compounds antagonized, to various extents, the effect of capsaicin in this assay. 3. All 6-halo-nordihydrocapsaicins behaved as competitive antagonists against human TRPV1 according to the corresponding Schild's plots, and were more potent than the corresponding 5-halogenated analogues. The iodo-derivatives were more potent than the bromo- and chloro-derivatives. 4. Using human recombinant TRPV1, 6-iodo-nordihydrocapsaicin (IC(50)=10 nM against 100 nM capsaicin) was about four times more potent than the prototypical TRPV1 antagonist, capsazepine, and was tested against capsaicin also on native TRPV1 in: (i) rat dorsal root ganglion neurons in culture; (ii) guinea-pig urinary bladder; and (iii) guinea-pig bronchi. In all cases, except for the guinea-pig bronchi, the compound was significantly more potent than capsazepine as a TRPV1 antagonist. 5. In conclusion, 6-iodo-nordihydrocapsaicin, a stable and easily prepared compound, is a potent TRPV1 antagonist and a convenient replacement for capsazepine in most of the in vitro preparations currently used to assess the activity of putative vanilloid receptor agonists. (literal)
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