title: Effect of a novel NK1 receptor selective antagonist (NKP608) on citric acid induced cough and airway obstruction.
abstract: The effects of an orally administered novel and selective NK1 antagonist, NKP608, on cough and airway obstruction, induced by citric acid in guinea pigs, were investigated. Guinea pigs were pre-treated with 0.03, 0.3 and 1 mg kg(-1) of NKP608, the NK2 antagonist, SR48968 or both 2 h prior to challenge with citric acid (0.6 M) for a 10 min period. Guinea pigs pre-treated with 0.03, 0.3 and 1mgkg(-1) of NKP608 exhibited a significant reduction of 77, 74 and 79%, respectively, in the numbers of cough compared to vehicle pre-treated animals (P<0.05). SR48968, 10 mg kg(-1), alone did not significantly affect the citric acid-induced cough but when co-administered with 1 mg kg(-1) of NKP608, there was a significant 90% reduction in cough. NKP608 did not significantly reduce the citric acid-induced increase in Penh at any of the doses used. SR48968 significantly reduced the citric acid induced airway obstruction by about 50%. However, when SR48968 was co-administered with NKP608, there was a greater (73%) decrease in the airway obstruction compared with SR48968 alone. These data show that NKP608, a selective NK1 receptor antagonist, is a potent inhibitor of citric acid induced cough in guinea pigs and may therefore have value in the therapy of clinical cough.
authors.affiliation: Department of Applied Therapeutics, Faculty of Pharmacy, Kuwait University, P.O. Box 24923, Safat 13110, Kuwait. ahmed.elhashim@hsc.huniv.edu.kw
authors.forename: A Z
authors.initials: AZ
authors.lastname: El-Hashim
authors.forename: D
authors.initials: D
authors.lastname: Wyss
authors.forename: C
authors.initials: C
authors.lastname: Lewis
mesh_terms: D000402:Airway Obstruction / Q000188:drug therapy*; D000818:Animals; D001549:Benzamides / Q000627:therapeutic use*; D019343:Citric Acid / Q000037:antagonists & inhibitors / Q000633:toxicity; D003371:Cough / Q000139:chemically induced / Q000517:prevention & control*; D006168:Guinea Pigs; D008297:Male; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines / Q000627:therapeutic use*; D010991:Plethysmography; D011804:Quinolines / Q000627:therapeutic use*
chemical_list: D001549:Benzamides; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D011804:Quinolines; C414491:quinoline-4-carboxylic acid (1-(3,5-bis-trifluoromethylbenzoyl)-2-(4-chlorobenzyl)piperidin-4-yl)amide; D019343:Citric Acid; C073839:SR 48968