The primary goal of pharmacological treatment in gastroparesis is to enhance gastric motility (prokinetics) and control symptoms (antiemetics). Metoclopramide remains the only FDA-approved medication specifically for gastroparesis. It acts as a dopamine D2 receptor antagonist and a 5-HT4 receptor agonist, promoting antral contractions. However, its use is limited by a "Black Box Warning" regarding the risk of tardive dyskinesia, a potentially irreversible movement disorder.

Other prokinetics include Domperidone, which has a lower risk of neurological side effects as it does not cross the blood-brain barrier, though it requires close cardiac monitoring due to potential QT-interval prolongation. Erythromycin, an antibiotic, is also used off-label as a potent motilin receptor agonist for acute flares. For an overview of the drug pipeline and emerging 5-HT4 agonists like prucalopride, the Gastroparesis Treatment Market research offers a technical analysis of current pharmaceutical developments.

Antiemetic therapy is used concurrently to manage nausea. Standard agents include ondansetron (a 5-HT3 antagonist) and phenothiazines. In refractory cases, neuromodulators such as tricyclic antidepressants (TCAs) may be used at low doses to alter visceral sensitivity. The challenge in pharmacological management is the "tachyphylaxis" effect, where the body becomes desensitized to prokinetic drugs over time, necessitating frequent adjustments to the treatment regimen.