title: Where are the new cough treatments: a debriefing of recent clinical proof-of-concept trials with the NOP agonist SCH 486757.
abstract: Cough continues to be one of the top reasons why patients seek medical attention from health care providers. The prescription antitussive market is dominated by opioids, such as codeine that produces inconsistent efficacy and is often accompanied by significant side effect liabilities. Consequently, cough represents an unmet medical need and an underserved market. Yet, against the backdrop of increasing cough research, the development of novel treatments has been exceptionally challenging with dextromethorphan being the last US drug approved for cough almost a half century ago. We support the position that an unambiguous and actionable 'road map' that clearly delineates the pathway forward for new cough suppressants from basic research to and beyond clinical proof-of-concept studies will be an important aspect for future success of this pharmacological class of drug. Pivotal to the establishment of such a road map will be the review of lessons learned from antitussive agents that have been recently progressed to proof-of-concept trials. In the present commentary, we briefly discuss observations and challenges pertaining to SCH 486757, a selective orally active NOP agonist that has recently advanced to human antitussive testing.
authors.affiliation: Bone, Respiratory, Immunology and Dermatology, Merck Research Laboratories, Kenilworth, NJ 07033-0539, USA. robbie.mcleod@spcorp.com
authors.forename: Robbie L
authors.initials: RL
authors.lastname: McLeod
authors.forename: Deen B
authors.initials: DB
authors.lastname: Tulshian
authors.forename: Jonathan
authors.initials: J
authors.lastname: Sadeh
mesh_terms: D000818:Animals; D000996:Antitussive Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D053961:Azabicyclo Compounds / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D003061:Codeine / Q000008:administration & dosage / Q000494:pharmacology; D003371:Cough / Q000188:drug therapy*; D003915:Dextromethorphan / Q000008:administration & dosage / Q000494:pharmacology; D004195:Disease Models, Animal; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D006168:Guinea Pigs; D006801:Humans; D018847:Opioid Peptides / Q000819:agonists / Q000378:metabolism; D011743:Pyrimidines / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D011957:Receptors, Opioid / Q000819:agonists; D000097629:Nociceptin
chemical_list: D000996:Antitussive Agents; D053961:Azabicyclo Compounds; D003061:Codeine; D003915:Dextromethorphan; D018847:Opioid Peptides; D011743:Pyrimidines; D011957:Receptors, Opioid; D000097629:Nociceptin; C549545:8-(bis(2-chlorophenyl)methyl)-3-(2-pyrimidinyl)-8-azabicyclo(3.2.1)octan-3-ol