Dual tachykinin NK1/NK2 antagonist DNK333 inhibits neurokinin A-induced bronchoconstriction in asthma patients

European Respiratory Journal

Volumn 23, Issue 1, 2004, Pages 76-81

  Joos, Guy F ^a   Vincken, W ^b   Louis, R ^c   Schelfhout, V J ^a   Wang, J H ^d   Shaw, M J ^d   Cioppa, G D ^d   Pauwels, R A ^a  

^a GHENT UNIVERSITY HOSPITAL   (Belgium)

^b UNIVERSITY HOSPITAL BRUSSELS   (Belgium)

^c UNIVERSITY OF LIÈGE   (Belgium)

^d Novartis Horsham Research Center   (United Kingdom)

Author keywords

Asthma; Bronchoconstriction; DNK333; Neurokinin A; Substance P; Tachykinins

Indexed keywords

DNK 333; NEUROKININ 1 RECEPTOR ANTAGONIST; NEUROKININ 2 RECEPTOR ANTAGONIST; NEUROKININ A; PLACEBO; SALBUTAMOL; TACHYKININ; TERBUTALINE; UNCLASSIFIED DRUG; BENZAMIDE DERIVATIVE; HETEROCYCLIC COMPOUND; TACHYKININ RECEPTOR;

ADULT; ARTICLE; ASTHMA; BRONCHODILATING ACTIVITY; BRONCHOSPASM; CLINICAL ARTICLE; CLINICAL TRIAL; CONCENTRATION RESPONSE; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; CROSSOVER PROCEDURE; DOUBLE BLIND PROCEDURE; DRUG BLOOD LEVEL; DRUG EFFICACY; FORCED EXPIRATORY VOLUME; HUMAN; IMMUNOPATHOGENESIS; LUNG FUNCTION TEST; MALE; PRIORITY JOURNAL; PROVOCATION TEST; RANDOMIZED CONTROLLED TRIAL; SINGLE DRUG DOSE; ADOLESCENT; DRUG ANTAGONISM; DRUG EFFECT; INHALATIONAL DRUG ADMINISTRATION; MIDDLE AGED; PATHOPHYSIOLOGY;

ADMINISTRATION, INHALATION; ADOLESCENT; ADULT; ASTHMA; AZA COMPOUNDS; BENZAMIDES; BRONCHOCONSTRICTION; CROSS-OVER STUDIES; DOUBLE-BLIND METHOD; HUMANS; MIDDLE AGED; NEUROKININ A; RECEPTORS, TACHYKININ;

EID: 0346505544     PISSN: 09031936     EISSN: None     Source Type: Journal    
DOI: 10.1183/09031936.03.00101902     Document Type: Article

References (24)

1. Joos GF, Germonpre PR, Pauwels RA. Role of tachykinins in asthma. Allergy 2000; 55: 321-337.
2. Naline E, Devillier P, Drapeau G, et al. Characterization of neurokinin effects and receptor selectivity in human isolated bronchi. Am Rev Respir Dis 1989; 140: 679-686.
3. Maggi CA, Patacchini R, Rovero P, Giachetti A. Tachykinin receptors and tachykinin receptor antagonists. J Anton Pharmacol 1993; 13: 23-93.
4. Advenier C, Lagente V, Boichot E. The role of tachykinin receptor antagonists in the prevention of bronchial hyper-responsiveness, airway inflammation and cough. Eur Respir J 1997; 10: 1892-1906.
5. Finney MJ, Karlsson MJA, Persson CGA. Effects of bronchoconstrictors and bronchodilators on a novel human small airway preparation. Br J Pharmacol 1985; 85: 29-36.
6. Advenier C, Naline E, Toty L, Bakdach H, Edmonds-Alt X, Vilain P, Breliere J-C, Le Fur G. Effects on the isolated human bronchus of SR 48968, a potent and selective nonpeptide antagonist of the neurokinin A (NK2) receptors. Am Rev Respir Dis 1992; 146: 1177-1181.
7. Advenier C, Joos G, Molimard M, Lagente V, Pauwels R. Role of tachykinins as contractile agonists of human airways in asthma. Clin Exp Allergy 1999; 29: 579-584.
8. Cheung D, Bel EH, Den Hartigh J, Dijkman JH, Sterk PJ. The effect of an inhaled neutral endopeptidase inhibitor, thiorphan, on airway responses to neurokinin A in normal humans in vivo. Am Rev Respir Dis 1992; 145: 1275-1280.
9. Cheung D, Timmers MC, Zwinderman AH, Den Hartigh J, Dijkman JH, Sterk PJ. Neutral endopeptidase activity and airway hyperresponsiveness to neurokinin A in asthmatic subjects in vivo. Am Rev Respir Dis 1993; 148: 1467-1473.
10. Maggi CA, Patacchini R, Rovero P, Santicioli P. Tachykinin receptors and noncholinergic bronchoconstriction in the guinea-pig isolated bronchi. Am Rev Respir Dis 1991; 144: 363-367.
11. Bertrand C, Nadel JA, Graf PD, Geppetti P. Capsaicin increases airflow resistance in guinea pigs in vivo by activating both NK2 and NK1 tachykinin receptors. Am Rev Respir Dis 1993; 148: 909-914.
12. Naline E, Molimard M, Regoli D, Emonds-Alt X, Bellamy J-F, Advenier C. Evidence for functional tachykinin NK1 receptors on human isolated small bronchi. Am J Physiol 1996; 271: L763-767.
13. Amadesi S, Moreau J, Tognetto M, et al. NK1 receptor stimulation causes contraction and mositol phosphate increase in medium-size human isolated bronchi. Am J Respir Crit Care Med 2001; 163: 1206-1211.
14. Mapp CE, Miotto D, Braccioni F, et al. The distribution of neurokinin-1 and neurokinin-2 receptors in human central airways. Am J Respir Crit Care Med 2000; 161: 207 215.
15. Joos GF, Pauwels RA. Tachykinin receptor antagonists: potential in airways diseases. Curr Opin Pharmacol 2001; 1: 235-241.
16. Joos GF, Van Schoor J, Kips JC, Pauwels RA. The effect of inhaled FK244, a tachykinin NK-1 and NK-2 receptor antagonist, on neurokinin A-induced bronchoconstriction in asthmatics. Am J Respir Crit Care Med 1996; 153: 1781-1784.
17. Van Schoor J, Joos G, Chasson B, Brouard R, Pauwels R. The effect of the NK2 receptor antagonist SR 48968 (saredutant) on neurokinin A-induced bronchoconstrction in asthmatics. Eur Respir J 1998; 12: 17 23.
18. Joos G, Schelfhout V, Van De Velde V, Pauwels R. The effect of the tachykinin NK2 receptor antagonist MEN 11420 (nepadutant) on neurokinin A-induced bronchoconstriction in patients with asthma. Am J Respir Crit Care Med 2001; 163: A628.
19. Gerspacher M, La Vecchia L, Mah R, et al. Dual neurokinin NK(1)/NK(2) antagonists: N-[(R,R)-(E)-1- arylmethyl-3-(2-oxo-azepan-3-yl)carbamoyl]allyl-N-methyl-3, 5-bis(trifluoromethyl)benzamides and 3-[N′-3,5-bis(trifluoro- methyl)benzoyl-N-arylmethyl-N′-methylhydrazino]-N-[(R)-2- oxo-azepan-3-yl]propionamides. Bioorg Med Chem Lett 2001; 11: 3081-3084.
20. Fozard JR, Mazzoni L, Hoshiko K. Effects of DNK333, a dual NK1/NK2 neurokinin receptor antagonist, on airway responsiveness induced by lipopolysaccharide or allergen challenge in the guinea-pig. Am J Respir Crit Care Med 2001; 163: A627.
21. Tough IR, Lewis CA, Fozard J, Cox HM. Dual and selective antagonism of neurokinin NK(1) and NK(2) receptor-mediated responses in human colon mucosa. Naunyn Schmiedeberg's Arch Pharmacol 2003; 367: 104-108.
22. Cockcroft DW, Killian DN, Mellon JJ, Hargreave FE. Bronchial reactivity to inhaled histamine: a method and clinical survey. Clin Allergy 1997; 7: 235-243.
23. Joos GF, Pauwels RA, Van Der Straeten ME. The effect of nedocromil sodium on the bronchoconstrictor effect of neurokinin A in subjects with asthma. J Allergy Clin Immunol 1989; 83: 663-668.
24. Van Schoor J, Joos GF, Pauwels RA. Effect of inhaled fluticasone on bronchial responsiveness to neurokinin A in asthma. Eur Respir J 2002; 19: 997-1002.