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Chemical Compound Review

Saredutant     N-[(2R)-4-(4-acetamido-4- phenyl-1...

Synonyms: CHEMBL308148, SureCN185911, CHEBI:215369, AC1L2XTE, LS-25204, ...
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Disease relevance of SR48968


Psychiatry related information on SR48968


High impact information on SR48968

  • Contraction evoked by NKA was inhibited by the nonpeptide NK2 antagonist SR 48968 but not by the nonpeptide NK1 receptor antagonist CP-96,345, tetrodotoxin, or atropine [9].
  • The existence of overlapping SR 48968 and NKA binding sites is also evident [10].
  • Furthermore, the selective nonpeptide NK2 receptor antagonist (S)-N-methyl-N-[4-acetylamino-4-phenylpiperidino)-2-(3,4-dichlorophenyl)butyl]benzamide (SR48968), which shows an antidepressant profile in animal studies, also enhanced PRAX-1 mRNA expression [11].
  • Furthermore, pretreatment with SR-48968, a selective antagonist of neurokinin-2 (NK(2)) receptor, inhibited more than 85% of the enhanced bronchomotor responses to CS challenge, but did not significantly reduce the airway hyperresponsiveness to ACh in Ova-sensitized guinea pigs [12].
  • In anaesthetized guinea pigs, it failed to inhibit the bronchoconstriction induced by citric acid when given alone but abolished it when combined with the tachykinin NK2 receptor antagonist, SR 48968 (saredutant) [13].

Chemical compound and disease context of SR48968


Biological context of SR48968

  • The combination had a significant additive effect against the bronchoconstriction, when compared with SR-48968 alone, and significantly inhibited the leakage of dye at the same airway levels as CP-96,345 [15].
  • After administration of SR 48968, inhalation of cold air reduced baseline airway tone [16].
  • Amino acid substitutions in the first and second extracellular segments and the second transmembrane segment led to substantial reduction in peptide affinity without affecting the affinity of antagonist SR48968 [17].
  • 4. One week after surgical interruption of the nerve supply to the knee joint, co-administration of FK888 and SR48968 (both at 10(-8) mol) now produced slight vasodilatation (6.7 +/- 4.6%; n = 9) which did not differ significantly from vehicle treatment [18].
  • In this more physiological situation, close intra-arterial injection of the combination of FK888 and SR48968 (both at 10(-8) mol) again elicited vasoconstriction (48.8 +/- 16.2% reduction in blood flow; n = 4) [18].

Anatomical context of SR48968

  • CP-96,345 (2 mg/kg, intravenous) but not SR-48968 (1.5 mg/kg, intravenous) significantly inhibited the leakage of dye at all airway levels except for trachea [15].
  • The selectivity of FK888 and SR 48968 was examined on NKA-induced contraction of ferret tracheal smooth muscle in vitro [19].
  • 5. Bronchoalveolar lavage studies performed at 25 h after the second OA provocation showed that SR48968 significantly inhibited the allergen-induced infiltration of neutrophils (P<0.05) and lymphocytes (P<0.01) in the airways [20].
  • In most neurons with input from the normal knee joint, SR48968 reduced dose-dependently the responses to noxious pressure with applied to the knee, and in approximately 50% of the neurons the responses to innocuous pressure [21].
  • A series of 14 mutants on nine selected residues of the human tachykinin NK(2) receptor was produced and stably transfected into CHO cells to investigate the binding of the peptide MEN 11420 and the nonpeptide SR 48968 antagonists [22].

Associations of SR48968 with other chemical compounds

  • This augmented response in CS-exposed animals was abolished after treatment with CP-99994 and SR-48968, the neurokinin (NK)-1 and NK-2 receptor antagonists, suggesting the involvement of tachykinins in chronic CS-induced airway hyperresponsiveness (AHR) [23].
  • The plasma extravasation produced by NKB in the lungs of NK(1) receptor knockout mice was unaffected by treatment with the NK(2) receptor antagonist SR48968 (3 mg kg(-1)), by the NK(3) receptor antagonists SR142801 (3 mg kg(-1)) and SB-222200 (5 mg kg(-1)) or by the cyclo-oxygenase (COX) inhibitor indomethacin (20 mg kg(-1)) [24].
  • In addition, the [Ca2+]i increase by 0.33 microM senktide, an NK3 receptor agonist, was inhibited by SR 142801 but not by SR 48968 [25].
  • The involvement of tachykinins in antigen-induced airway hyperresponsiveness (AHR) was characterized pharmacologically in guinea-pigs sensitized to ovalbumin with antagonists of tachykinin NK1 and NK2 receptors, namely SR 140333 and SR 48968, respectively [26].
  • NKA stimulated proliferation of prostate epithelial cells without any apoptotic effect, which was attenuated by SR-48968 [27].

Gene context of SR48968


Analytical, diagnostic and therapeutic context of SR48968


  1. The NK-2 receptor antagonist SR 48968C does not improve adenosine hyperresponsiveness and airway obstruction in allergic asthma. Kraan, J., Vink-Klooster, H., Postma, D.S. Clin. Exp. Allergy (2001) [Pubmed]
  2. Differential roles of neurokinin 1 and neurokinin 2 receptors in the development and maintenance of heat hyperalgesia induced by acute inflammation. Sluka, K.A., Milton, M.A., Willis, W.D., Westlund, K.N. Br. J. Pharmacol. (1997) [Pubmed]
  3. The role of sensorial neuropeptides in the edematogenic responses mediated by B(1) agonist des-Arg(9)-BK in rats pre-treated with LPS. Ferreira, P.K., Campos, M.M., Calixto, J.B. Regul. Pept. (2000) [Pubmed]
  4. Neurokinin-1 and neurokinin-2 antagonism inhibits long-term acid fog-induced airway hyperresponsiveness. Teramoto, S., Tanaka, H., Kaneko, S., Abe, S. Chest (2003) [Pubmed]
  5. Tachykinin NK2 receptors further characterized in the lung with nonpeptide receptor antagonists. Advenier, C. Can. J. Physiol. Pharmacol. (1995) [Pubmed]
  6. Effects of SR48968, a selective non-peptide NK2 receptor antagonist on emotional processes in rodents. Griebel, G., Perrault, G., Soubrié, P. Psychopharmacology (Berl.) (2001) [Pubmed]
  7. Use of non-peptide tachykinin receptor antagonists to substantiate the involvement of NK1 and NK2 receptors in a spinal nociceptive reflex in the rat. Picard, P., Boucher, S., Regoli, D., Gitter, B.D., Howbert, J.J., Couture, R. Eur. J. Pharmacol. (1993) [Pubmed]
  8. Selective blockade of NK2 or NK3 receptors produces anxiolytic- and antidepressant-like effects in gerbils. Salomé, N., Stemmelin, J., Cohen, C., Griebel, G. Pharmacol. Biochem. Behav. (2006) [Pubmed]
  9. Tachykinins contract the circular muscle of the human esophageal body in vitro via NK2 receptors. Huber, O., Bertrand, C., Bunnett, N.W., Pellegrini, C.A., Nadel, J.A., Debas, H.T., Geppetti, P. Gastroenterology (1993) [Pubmed]
  10. Interaction of Met297 in the seventh transmembrane segment of the tachykinin NK2 receptor with neurokinin A. Labrou, N.E., Bhogal, N., Hurrell, C.R., Findlay, J.B. J. Biol. Chem. (2001) [Pubmed]
  11. Expression profile and up-regulation of PRAX-1 mRNA by antidepressant treatment in the rat brain. Chardenot, P., Roubert, C., Galiègue, S., Casellas, P., Le Fur, G., Soubrié, P., Oury-Donat, F. Mol. Pharmacol. (2002) [Pubmed]
  12. Airway hyperresponsiveness to cigarette smoke in ovalbumin-sensitized guinea pigs. Wu, Z.X., Zhou, D., Chen, G., Lee, L.Y. Am. J. Respir. Crit. Care Med. (2000) [Pubmed]
  13. Involvement of tachykinin NK3 receptors in citric acid-induced cough and bronchial responses in guinea pigs. Daoui, S., Cognon, C., Naline, E., Emonds-Alt, X., Advenier, C. Am. J. Respir. Crit. Care Med. (1998) [Pubmed]
  14. Receptor subtypes involved in tachykinin-mediated edema formation. Alves, R.V., Campos, M.M., Santos, A.R., Calixto, J.B. Peptides (1999) [Pubmed]
  15. Involvement of tachykinin receptors (NK1 and NK2) in sodium metabisulfite-induced airway effects. Sakamoto, T., Tsukagoshi, H., Barnes, P.J., Chung, K.F. Am. J. Respir. Crit. Care Med. (1994) [Pubmed]
  16. Endogenous nitric oxide inhibits bronchoconstriction induced by cold-air inhalation in guinea pigs: role of kinins. Yoshihara, S., Nadel, J.A., Figini, M., Emanueli, C., Pradelles, P., Geppetti, P. Am. J. Respir. Crit. Care Med. (1998) [Pubmed]
  17. Identification of residues involved in ligand binding to the neurokinin-2 receptor. Huang, R.R., Vicario, P.P., Strader, C.D., Fong, T.M. Biochemistry (1995) [Pubmed]
  18. Tachykinin regulation of basal synovial blood flow. Ferrell, W.R., Lockhart, J.C., Karimian, S.M. Br. J. Pharmacol. (1997) [Pubmed]
  19. 'Sensory-efferent' neural control of mucus secretion: characterization using tachykinin receptor antagonists in ferret trachea in vitro. Ramnarine, S.I., Hirayama, Y., Barnes, P.J., Rogers, D.F. Br. J. Pharmacol. (1994) [Pubmed]
  20. Role of tachykinin NK2-receptor activation in the allergen-induced late asthmatic reaction, airway hyperreactivity and airway inflammatory cell influx in conscious, unrestrained guinea-pigs. Schuiling, M., Zuidhof, A.B., Meurs, H., Zaagsma, J. Br. J. Pharmacol. (1999) [Pubmed]
  21. The role of spinal neurokinin-2 receptors in the processing of nociceptive information from the joint and in the generation and maintenance of inflammation-evoked hyperexcitability of dorsal horn neurons in the rat. Neugebauer, V., Rumenapp, P., Schaible, H.G. Eur. J. Neurosci. (1996) [Pubmed]
  22. Molecular determinants of peptide and nonpeptide NK-2 receptor antagonists binding sites of the human tachykinin NK-2 receptor by site-directed mutagenesis. Giolitti, A., Cucchi, P., Renzetti, A.R., Rotondaro, L., Zappitelli, S., Maggi, C.A. Neuropharmacology (2000) [Pubmed]
  23. Chronic smoking enhances tachykinin synthesis and airway responsiveness in guinea pigs. Kwong, K., Wu, Z.X., Kashon, M.L., Krajnak, K.M., Wise, P.M., Lee, L.Y. Am. J. Respir. Cell Mol. Biol. (2001) [Pubmed]
  24. Neurokinin B induces oedema formation in mouse lung via tachykinin receptor-independent mechanisms. Grant, A.D., Akhtar, R., Gerard, N.P., Brain, S.D. J. Physiol. (Lond.) (2002) [Pubmed]
  25. Further identification of neurokinin receptor types and mechanisms of calcium signaling evoked by neurokinins in the murine neuroblastoma C1300 cell line. Fukuhara, S., Mukai, H., Kako, K., Nakayama, K., Munekata, E. J. Neurochem. (1996) [Pubmed]
  26. Prevention by the tachykinin NK2 receptor antagonist, SR 48968, of antigen-induced airway hyperresponsiveness in sensitized guinea-pigs. Boichot, E., Germain, N., Lagente, V., Advenier, C. Br. J. Pharmacol. (1995) [Pubmed]
  27. Effect of neurokinins on canine prostate cell physiology. Walden, P.D., Marinese, D., Srinivasan, D., Tzoumaka, E., Syyong, H.T., Ford, A.P., Bhattacharya, A. Prostate (2005) [Pubmed]
  28. PAR-2 agonists induce contraction of murine small intestine through neurokinin receptors. Zhao, A., Shea-Donohue, T. Am. J. Physiol. Gastrointest. Liver Physiol. (2003) [Pubmed]
  29. Role of NK1 and NK2 receptors in mouse gastric mechanical activity. Mulè, F., Amato, A., Vannucchi, M.G., Faussone-Pellegrini, M.S., Serio, R. Br. J. Pharmacol. (2006) [Pubmed]
  30. Analysis of the inflammatory response induced by substance P in the mouse pleural cavity. Fröde-Saleh, T.S., Calixto, J.B., Medeiros, Y.S. Peptides (1999) [Pubmed]
  31. In vitro characterization of tachykinin NK2-receptors modulating motor responses of human colonic muscle strips. Croci, T., Aureggi, G., Manara, L., Emonds-Alt, X., Le Fur, G., Maffrand, J.P., Mukenge, S., Ferla, G. Br. J. Pharmacol. (1998) [Pubmed]
  32. Characterization of NK3 receptors in rabbit isolated iris sphincter muscle. Medhurst, A.D., Parsons, A.A., Roberts, J.C., Hay, D.W. Br. J. Pharmacol. (1997) [Pubmed]
  33. Postjunctional inhibitory effect of the NK2 receptor antagonist, SR 48968, on sensory NANC bronchoconstriction in the guinea-pig. Lou, Y.P., Lee, L.Y., Satoh, H., Lundberg, J.M. Br. J. Pharmacol. (1993) [Pubmed]
  34. Role of tachykinins in castor oil diarrhoea in rats. Croci, T., Landi, M., Emonds-Alt, X., Le Fur, G., Maffrand, J.P., Manara, L. Br. J. Pharmacol. (1997) [Pubmed]
  35. Respiratory actions of tachykinins in the nucleus of the solitary tract: characterization of receptors using selective agonists and antagonists. Mazzone, S.B., Geraghty, D.P. Br. J. Pharmacol. (2000) [Pubmed]
  36. Characterization of the antibronchoconstrictor activity of MEN 11420, a tachykinin NK2 receptor antagonist, in guinea-pigs. Tramontana, M., Patacchini, R., Giuliani, S., Lippi, A., Lecci, A., Santicioli, P., Criscuoli, M., Maggi, C.A. Eur. J. Pharmacol. (1998) [Pubmed]
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