Lessons from pharmacogenetics and metoclopramide: toward the right dose of the right drug for the right patient.

The prokinetic effect of metoclopramide is mediated through the blockade of enteric (neuronal and muscular) inhibitory dopamine D2 receptors, and metoclopramide has the ability to stimulate 5-HT3 and 5-HT4 receptors (2). Metoclopramide also exerts inhibitory effects on D2 receptors centrally (located outside the blood-brain barrier), and these contribute to its antiemetic effect. Metoclopramide binds to α1D adrenergic receptors, and there is a functional interaction between dopamine and adrenergic receptors; however, the precise mechanism resulting in prokinetic action is unclear.