Novel therapeutic targets for enteric nervous system disorders.
There is a large unmet need for effective drugs for the treatment of gastrointestinal disorders, notably irritable bowel syndrome, functional dyspepsia and gastroesophageal reflux disease. The market value for an effective irritable bowel syndrome therapeutic agent is estimated at over US10 billion dollars per annum. Each of these disorders seems to have a neural component, involving the intrinsic innervation of the gastrointestinal system, its extrinsic innervation or both. The substantially improved understanding of the transmitters, receptors and ion channels of enteric neurons that now exists has led to targeted therapy. The most promising targets so far have been 5-hydroxytryptamine receptors. Other targets include opioid, cholecystokinin, tachykinin, cannabinoid, corticotropin-releasing factor and protease-activated receptors. Ion channels are also potential targets. Although current knowledge has yet to be adequately translated into effective therapies, each of the targets holds promise for the future that might be realized as new compounds with appropriate receptor specificity and pharmacodynamic profiles are developed.
De Giorgio
Roberto
R
Department of Internal Medicine & Gastroenterology, University of Bologna, Bologna, Italy.
Barbara
Giovanni
G
Furness
John B
JB
Tonini
Marcello
M
D000818:Animals; D005767:Gastrointestinal Diseases / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D009422:Nervous System Diseases / Q000188:drug therapy* / Q000378:metabolism; D044462:Receptors, Proteinase-Activated / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000627:therapeutic use; D017366:Serotonin Receptor Agonists / Q000627:therapeutic use
D044462:Receptors, Proteinase-Activated; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists