Prokinetic targets

Prokinetic targets represent a diverse group of molecular entities, primarily G protein-coupled receptors and enzymes, that regulate the motility of the gastrointestinal (GI) tract. The most prominent targets include the serotonin 5-HT4 receptor, the dopamine D2 receptor, the motilin receptor, and the ghrelin receptor, as well as the enzyme acetylcholinesterase. These targets are primarily located within the enteric nervous system and on GI smooth muscle cells, where they modulate the release of neurotransmitters like acetylcholine to coordinate peristaltic contractions. Pharmacological modulation of these targets—typically through 5-HT4 agonism or D2 antagonism—is a mainstay in the treatment of motility disorders such as gastroparesis, functional dyspepsia, and chronic constipation. However, the clinical utility of many prokinetic agents has been historically limited by significant safety issues, including cardiovascular risks such as QT prolongation and central nervous system side effects like extrapyramidal symptoms.

Other names

Gastroprokinetic targetsGI motility targetsProkinetic receptorsGastrointestinal motility targets

Agonism of 5-HT4 receptors, antagonism of D2 receptors, agonism of motilin receptors, agonism of ghrelin receptors, and inhibition of acetylcholinesterase.