Pharmacological stimulation of gastrointestinal motility: where we are and where are we going?

Drugs affecting gastrointestinal motility have become valuable in the management of a number of diseases. Medications that enhance the transit of material through the gastrointestinal tract are called prokinetics. Although symptom improvement can be seen in a variety of motility disorders, these medications have not shown a selective benefit for a particular motility disturbance or symptom complex. This class of drugs includes several subclasses, each with a distinct mechanism of action. Amongst the existing prokinetic compounds, dopamine antagonists, on the one hand, and cholinomimetic drugs, on the other hand, should be distinguished. Since compounds endowed with dopamine antagonism have the disadvantage of causing neuroendocrine side effects and/or extrapyramidal dyskinetic reactions (seen especially after metoclopramide), the recently developed non-cholinergic non-antidopaminergic compound, cisapride, seems to be the most effective one. Its main mechanism of action is considered to be the stimulation of myenteric cholinergic nerves with consequent increase of acetylcholine release. Recent evidence suggests that blockade of CCK receptors and stimulation of motilin receptors are also promising avenues to increase gastrointestinal motility. Since drugs acting on 5-HT receptors are presently the best available motor-stimulating compounds, new derivatives are being developed as gastrokinetic drugs. Although the long-acting somatostatin analog, octreotide, and the GnRH agonist, leuprolide, have shown prokinetic properties in particular clinical conditions, their widespread use cannot be recommended at present. Further work is needed to determine the predictive value of objective abnormalities for the efficacy of a drug in the individual patient. This is the crucial point to define a rational strategy in clinical practice, especially to establish if functional investigation is needed before a prokinetic drug be given.