Emerging drugs for the treatment of gastroparesis

Gastroparesis presents with symptoms of gastric retention with findings of delayed gastric emptying on diagnostic testing. Manifestations of gastroparesis are disabling in severe cases and lead to significant health resource utilization. Current therapies often are ineffective, may exhibit tolerance on chronic administration or produce prominent side effects in large patient subsets.

This review assessed literature on drugs with theoretical efficacy in gastroparesis including medications that accelerate gastric emptying, reduce nausea and vomiting, or act as neuromodulators to reduce gastric sensitivity. Numerous agents exhibit diverse actions to modify gastric sensorimotor function in animal models; however, few medications are in controlled testing in gastroparesis. Prokinetic drugs with promise for this condition include investigational serotonin 5-HT4 agonists, motilin agonists, dopamine D2 antagonists, ghrelin agonists and an agent with combined muscarinic antagonist and acetylcholinesterase inhibitory effects. Other antiemetics and complementary and alternative formulations may be effective for some symptoms.

Development of effective novel therapies of gastroparesis without the neurotoxicity and cardiac arrhythmogenic effects of current agents will mandate a better definition of the gastric and extragastric factors responsible for the pathogenesis of the varied clinical manifestations of this disorder.