Antitussive activity of the tachykinin NK1 receptor antagonist, CP-99994, in dogs.
CP-99994 [(+)-(2S,3S)-3-(2-methoxybenzylamino)-2-phenylpiperidine] is a selective tachykinin NK(1) receptor antagonist that inhibits cough in guinea pigs and cats. This study examined the antitussive effects of CP-99994 in dogs produced by mechanical stimulation of the intrathoracic trachea. CP-99994 (10 mg/kg, p.o.) inhibited cough frequency by 52% at 2 h, 31% at 6 h and by 21% at 24 h. Cough amplitude was inhibited by 45% at 6 h but unchanged at 2 and 24 h after CP-99994. Plasma levels of CP-99994 were highest at 2 h (75+/-26 ng/ml) and fell to 22+/-6 ng/ml at 6 h. These results demonstrate antitussive activity of CP-99994 in dogs at a dose proven to antagonize tachykinin NK(1) receptors in this species.
Chapman
Richard W
RW
Schering-Plough Research Institute, 2015 Galloping Hill Road, MS K15-1-1650, Kenilworth, NJ 07033, USA. richard.chapman@spcorp.com
House
Aileen
A
Liu
Fei
F
Celly
Chander
C
Mei
Hong
H
Hey
John A
JA
D000818:Animals; D000996:Antitussive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D003371:Cough / Q000188:drug therapy* / Q000503:physiopathology; D004285:Dogs; D008297:Male; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use*; D018040:Receptors, Neurokinin-1 / Q000502:physiology
D000996:Antitussive Agents; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D018040:Receptors, Neurokinin-1; C080755:3-(2-methoxybenzylamino)-2-phenylpiperidine