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

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 NK 1 and NK 2 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 [ 3 H]substance P (IC 50 = 3.3 ± 1.8 × 10 −7 M) from guinea-pig bronchial tachykinin NK 1 sites. The displacement of [ 125 I]neurokinin A, a specific tachykinin NK 2 receptor ligand, needed higher concentrations (IC 50 = 4.5 ± 0.6 × 10 −6 M). It is concluded that vapreotide possesses an antagonist activity on guinea-pig tachykinin NK 1 receptors; the involvement in its analgesic action is discussed.