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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

In vivo and in vitro pharmacology of SR 48,968, a non-peptide tachykinin NK2 receptor antagonist.

The activity of SR 48,968, a novel non-peptide antagonist of tachykinin NK2 receptors was evaluated in vitro in several bioassays for the NK2 receptor (rabbit pulmonary artery, rabbit bronchus, hamster trachea, rat vas deferens) and compared to that of the peptide antagonists, MEN 10,376, L 659,877 and MDL 29,913. SR 48,968 behaved as a potent and competitive antagonist in the four isolated preparations (pA2 values between 8.3 and 9.6 in different preparations), being more potent (about 10 times) in the rabbit pulmonary artery and rabbit bronchus than in the hamster trachea or rat vas deferens. The antagonistic profile of SR 48,968 resembled that of MEN 10,376, and contrasted with those of L 659,877 and MDL 29,913 which were distinctly more potent on the hamster trachea and rat vas deferens. In vivo, SR 48,968 (0.1 mumol/kg i.v.) blocked the contraction of rat urinary bladder stimulated by [beta Ala8]neurokinin A-(4-10) (NK2 receptor agonist) without affecting that produced by [Sar9]substance P sulfone (NK1 receptor agonist). The hypotension and salivary secretion produced by the latter agonist were not modified by SR 48,968. In contrast, (+/-)-CP 96,345 (10 mumol/kg i.v.) blocked bladder contraction, salivary secretion and hypotensive responses elicited by the NK1 receptor agonist while leaving unaffected the bladder contraction produced by the NK2 receptor agonist. SR 48,968 is a potent and competitive antagonist of the tachykinin NK2 receptor with a limited but distinct ability to discriminate between putative subtypes/species variants of the NK2 receptor. The high potency and selectivity of SR 48,968 make this novel compound an important tool for studying the distribution and function of tachykinin NK2 receptors.[1]


  1. In vivo and in vitro pharmacology of SR 48,968, a non-peptide tachykinin NK2 receptor antagonist. Maggi, C.A., Patacchini, R., Giuliani, S., Giachetti, A. Eur. J. Pharmacol. (1993) [Pubmed]
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