16.02.2 Prokinetic Agents

The contraction phase of peristalsis is due to release of acetylcholine from excitatory motor neurones. Prokinetic agents modify this release of acetylcholine. For instance, dopamine acts at D₂-receptors to inhibit the release of acetylcholine from the enteric nervous system (figure 16.1).

Figure 16.1 Dopamine inhibits gut motility (Copyright QUT, Sheila Doggrell)

Antagonists at D₂-receptors will prevent this effect of dopamine, to increase the release of acetylcholine and increase gut motility.

Domperidone is a selective dopamine D₂-receptor antagonist that prevents the inhibitory effect of dopamine on acetylcholine release, which leads to an increased release of acetylcholine locally, which is prokinetic. Domperidone is used in GERD and gastroparesis.

5-Hydroxytryptamine (5-HT), acts at the 5-HT₄ receptor, to stimulate the enteric nervous system (Figure 16.2).

Figure 16.2 5-HT stimulates gut motility (Copyright QUT, Sheila Doggrell)

Prucalopride is a selective 5-HT4 receptor agonist that acts as a prokinetic. It is a relatively new drug. Prucalopride is used in chronic constipation, when the standard agents are not working.

Metoclopramide is prokinetic by combining these two actions. Thus, metoclopramide acts as an antagonist at dopamine D₂-receptors, and an agonist at 5-HT₄-receptors, to stimulate the gastrointestinal tract. Metoclopramide is used in the treatment of GERD and gastroparesis.