In vitro and in vivo evidence for a tachykinin NK1 receptor antagonist effect of vapreotide, an analgesic cyclic analog of somatostatin

Florence Bétoin, Charles Advenier, Véronique Fardin, George Wilcox, Jeannine Lavarenne, Alain Eschalier

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Vapreotide, a long-acting somatostatin analog, possesses an analgesic effect. The purpose of this work was to determine a tachykinergic involvement. Vapreotide reduced substance P-induced biting and scratching in mice. This inhibitory effect of substance P action was confirmed by experiments performed on the bronchial apparatus of guinea-pigs known to possess tachykinin NK1 and NK2 receptors. (i) Vapreotide reduced the substance P-induced plasmatic exudation. (ii) It inhibited selectively the tachykinin-dependent second contractile phase induced by electrical field stimulation of isolated bronchi. (iii) It shifted to the right the concentration-effect curve of substance P-induced contraction of isolated main bronchi. The peptide displaced [3H]substance P (IC50 = 3.3 ± 1.8 × 10-7 M) from guinea-pig bronchial tachykinin NK1 sites. The displacement of [125I]neurokinin A, a specific tachykinin NK2 receptor ligand, needed higher concentrations (IC50 = 4.5 ± 0.6 × 10-6 M). It is concluded that vapreotide possesses an antagonist activity on guinea-pig tachykinin NK1 receptors; the involvement in its analgesic action is discussed.

Original languageEnglish (US)
Pages (from-to)241-249
Number of pages9
JournalEuropean Journal of Pharmacology
Volume279
Issue number2-3
DOIs
StatePublished - Jun 12 1995

Bibliographical note

Funding Information:
This work has been supported by a grant from Debiopharm S.A. Lausanne and l'Association pour la Recherche sur le Cancer, Paris. We are grateful to C. Garret (Rh6ne-Poulenc-Rorer, Paris) for his help.

Keywords

  • Airway
  • Binding
  • Somatostatin analog
  • Substance P
  • Tachykinin NK receptor
  • Tachykinin NK receptor
  • Vapreotide

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