Evolving Therapies

Some reports have shown that diabetic patients with gas-troparesis have abnormally high pyloric sphincter pressures. This has lead to the concept of "pyloric spasm" and the idea that therapies aimed at relaxing the pyloric sphincter could improve gastric emptying. The use of sildenafil and local botulinum toxin A injections have been proposed to address this particular pathophysiology. Preliminary reports suggest that 100 to 200 Units of botulinum toxin injected directly into the pylorus endoscopically is effective in temporarily relieving symptoms in idiopathic and diabetic gastroparesis, although further study is needed (Ezzeddine et al, 2002). It would seem best suited to the setting of an accidental vagal nerve injury accompanying fundoplication or esophageal surgery. Here it would simulate the effects of a pyloroplasty without the necessity for surgery. Since repeated administration will be required, formulation and administration issues may preclude its use as a first line therapy. Sildenafil (Viagra) is a phosphodiesterase inhibitor that leads to increased levels of nitric oxide in the pylorus and hence relaxation. It has been shown to increase gastric emptying in animal models. Its use for gastroparesis in humans is under investigation. A long-acting form with once daily dosing is also being introduced.

GM-611 (Mitemcinal, Chugai Pharmaceutical Company) is a macrolide that, like erythromycin, binds to the motilin receptor and stimulates enteric contractility, but does not have antimicrobial properties. It is currently in phase II trials and has been shown to increase gastric motility and gastric emptying in animal models as well as patients with diabetic gastroparesis. Results of these treatment trials on gastroparesis will be available in the near future.

Mosapride (Takeda Pharmaceutical Company) is an investigational agent and is a 5-HT4 agonist. It has been shown to have stimulatory effects throughout the human GI tract and has less potential for cardiac arrhythmia than its predecessor, Propulsid. It may become a useful agent in the treatment of gastroparetic patients and gastroesophageal reflux and these trials are currently being conducted.

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