title: Early investigational therapeutics for gastrointestinal motility disorders: from animal studies to Phase II trials.
abstract: BACKGROUND
  The most common gastrointestinal disorders that include evidence of dysmotility include: gastroparesis, the lower functional gastrointestinal disorders associated with altered bowel function (such as chronic [functional] diarrhea, chronic idiopathic constipation) and opioid-induced constipation. These conditions, which are grouped as gastrointestinal motility and functional disorders, are characterized by abnormal motor, sensory or secretory functions that alter bowel function and result in a significant disease burden, since currently available treatments do not completely alleviate symptoms. New drugs are being developed for these disorders, targeting mechanisms involved in the pathophysiology of these diseases, specifically, motor function, intestinal secretion and bile acid modulation.
  
  
  METHODS
  The article provides a brief overview of motility disorders and the drugs approved and currently available for these indications. It also provides an evaluation of the efficacy, safety and possible mechanisms of the drugs currently under investigation for the treatment of gastroparesis, chronic diarrhea, chronic idiopathic constipation and opioid-induced constipation, based on animal to Phase II studies. Medications with complete Phase III trials are excluded from this discussion.
  
  
  CONCLUSIONS
  Treatment of gastrointestinal motility disorders requires the understanding of the pathophysiological mechanisms, biomarkers to identify subgroups of these disorders and robust pharmacological studies from animal to Phase II studies. These are prerequisites for the development of efficacious medications and individualizing therapy in order to enhance the treatment of these patients.
authors.affiliation: Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), Mayo Clinic , 200 First St. S.W., Charlton Bldg, Rm. 8-110, Rochester, MN 55905 , USA +1 507 266 2305 ; camilleri.michael@mayo.edu.
authors.forename: Nelson
authors.initials: N
authors.lastname: Valentin
authors.forename: Andres
authors.initials: A
authors.lastname: Acosta
authors.forename: Michael
authors.initials: M
authors.lastname: Camilleri
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D017322:Clinical Trials, Phase II as Topic; D015195:Drug Design; D015507:Drugs, Investigational / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D005767:Gastrointestinal Diseases / Q000188:drug therapy* / Q000503:physiopathology; D005769:Gastrointestinal Motility / Q000187:drug effects*; D006801:Humans
chemical_list: D015415:Biomarkers; D015507:Drugs, Investigational
keywords: acetylcholine; agonist; antagonist; bile acids; ghrelin; motilin; opioids; pharmacology; receptor; serotonin