Effect of a novel NK1 receptor selective antagonist (NKP608) on citric acid induced cough and airway obstruction.
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.
El-Hashim
A Z
AZ
Department of Applied Therapeutics, Faculty of Pharmacy, Kuwait University, P.O. Box 24923, Safat 13110, Kuwait. ahmed.elhashim@hsc.huniv.edu.kw
Wyss
D
D
Lewis
C
C
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*
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