Esophageal pharmacology and treatment of primary motility disorders

Swallowing is a complex mechanism based on the coordinated collaboration of tongue, pharynx and esophagus, Disturbances of this interplay or disorders of one or several of these components lead to dysphagia, noncardiac chest pain or regurgitation, The major primary esophageal motility disorders - ac halasia, diffuse esophageal spasm, hypercontractile esophagus ('nutcracker esophagus') and non-specific motility disorder - are of unknown etiology, O ther esophageal diseases, such as cervical diverticula or gastroesophageal reflux disease, might also be caused by a primary esophageal motility disor der. Medical treatment of esophageal disorders with esophageal hyper- or dy smotility requires agents that reduce esophageal contractile force (anticho linergic agents, nitrates, calcium antagonists), Despite the beneficial eff ect of the various drugs on esophageal motility parameters, the clinical be nefit of medical treatment of esophageal motility disorders is rather disap pointing. Calcium channel antagonist, alone or in combination with antichol inergics or nitrates, can be used as a medical trial, especially in mild ac halasia, However, medical therapy is clearly inferior to pneumatic balloon dilation therapy. Recently, botulinum toxin injection was suggested as a th erapeutic option in achalasia patients with good results on lower esophagea l sphincter pressure (LESP) and symptom scores that were similar to the res ults achieved by pneumatic balloon dilation. Hypercontractile esophagus sho ws a good manometric response to calcium channel antagonists, but only litt le clinical effect in terms of improvement of symptoms. Diffuse esophageal spasm is a relatively rare disease and few clinical studies are available. The use of calcium channel antagonists can be beneficial, at least in some patients with diffuse esophageal spasm. From clinical and epidemiological s tudies, there is some evidence of a 'psychological' component in the pathog enesis or perception of esophageal symptoms. There is some clinical benefit from centrally acting drugs such as benzodiazepines or antidepressants, With the exception of botulinum toxin for achalasia, medical therapy of pri mary esophageal motility disorders is rather limited and the clinical resul ts are poor. Further understanding of esophageal pathophysiology as well as development of new receptor-selective drugs might increase our chances of a successful treatment of primary esophageal motility disorders.