Exploring SCH 225288: A NOP Receptor Agonist's Antitussive Efficacy in Animal Models

Nociceptin/orphanin FQ (N/OFQ) is a peptide that binds to the NOP receptor and has been shown to inhibit cough in experimental settings. SCH 225288, a nonpeptide NOP receptor agonist, is being explored for its potential as a new treatment for cough. The compound's selectivity was characterized in human receptor binding assays, and its antitussive activity was investigated across three distinct cough models.

In the guinea pig capsaicin cough model, SCH 225288 demonstrated a dose-dependent suppression of cough that lasted for up to 6 hours post-administration. The effect was specific, as it was blocked by the NOP antagonist J113397 and not by the opioid receptor antagonist naltrexone. In anesthetized cats, SCH 225288 reduced cough number and abdominal electromyographic (EMG) amplitudes when administered intravenously or intra-arterially, with no significant impact on parasternal EMG activity.

Additionally, SCH 225288 was evaluated in a canine Bordetella bronchiseptica disease model. The compound showed a trend towards an antitussive effect, contrasting with butorphanol, which lacked antitussive activity in the same model.

The study concludes that SCH 225288 is a potent antitussive agent in animal cough models, suggesting that NOP agonists could offer a new therapeutic strategy for cough treatment without the side effects commonly associated with opioid-based antitussives.