The efficacy of a NOP1 agonist (SCH486757) in subacute cough.
Currently, opiates are widely used as antitussives but have substantial side effects. Recently, it has been proposed that NOP1 receptor agonists may be useful as a novel approach to cough suppression. Therefore, we compared the effect of NOP1 receptor agonist SCH486757 with matched placebo and codeine in a multicentre, double-blind, parallel-group study in patients with subacute cough. The primary outcome was change in cough severity scores, with the key secondary outcome change in objective daytime cough counts. We studied 91 subjects with subacute cough [59 (65%) female, median age = 41(range = 18-64) years, and median cough duration = 33 (range = 16-99) days]. Subjects were randomised to receive either SCH486757 100 mg, codeine 30 mg, or matched placebo twice daily for 5 days. Cough severity was scored throughout using a diary card and objective cough frequency recorded for 8 h at baseline and on the first and last treatment days. There were no significant differences in changes in average cough severity scores from baseline to treatment between SCH486757 and placebo [mean change = -0.57 (-30.1%) vs. mean change = -0.49 (-19.7%); P = 0.56] or between codeine and placebo [mean change = -0.72 (-33.2%); P = 0.07 compared to placebo). Changes in objective cough counts also showed no differences between the three treatment groups. There were some hints of possible limited antitussive efficacy with SCH486757. Unfortunately, the maximum clinical dose is limited by its tendency to produce somnolence. If the therapeutic ratio of NOP1 agonists could be improved, these drugs may still prove to contain effective antitussives.
Woodcock
Ashley
A
Respiratory Research Group, University of Manchester, Oxford Road, Manchester M13 9PL, UK.
McLeod
Robbie L
RL
Sadeh
Jonathan
J
Smith
Jaclyn A
JA
D000208:Acute Disease; D000328:Adult; D000704:Analysis of Variance; D000996:Antitussive Agents / Q000627:therapeutic use*; D053961:Azabicyclo Compounds / Q000627:therapeutic use*; D003371:Cough / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D057194:Intention to Treat Analysis; D008297:Male; D008875:Middle Aged; D018847:Opioid Peptides; D011743:Pyrimidines / Q000627:therapeutic use*; D011957:Receptors, Opioid; D012720:Severity of Illness Index; D055815:Young Adult; D000094942:Nociceptin Receptor
C549545:8-(bis(2-chlorophenyl)methyl)-3-(2-pyrimidinyl)-8-azabicyclo(3.2.1)octan-3-ol; D000996:Antitussive Agents; D053961:Azabicyclo Compounds; D018847:Opioid Peptides; D011743:Pyrimidines; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; C000722283:OPRL1 protein, human