Metoclopramide

Abstract Metoclopramide, a benzamide derivative, is used as an antiemetic and for disorders of gastric motility. The drug se lectively blocks both D2 dopamine receptors (centrally and in the gut) (8) and central serotonin 5-HT3 receptors (32). Antiemetic activity may be due to blockade of both of these receptors in the chemoreceptor trigger zone in the medulla oblongata. The drug is a potent antiemetic and is useful in treating cancer patients receiving chemotherapy (23). In the gut, metoclopramide increases gastric and small-bowel (but not large-bowel) motility, relaxes the pyloric sphincter, and increases resting tone in the lower esophageal sphincter (8). The mechanism by which metoclopramide effects these changes in the gut is not well understood, but it appears to be mediated by enhanced cholinergic activity in that the effects are blocked by anticholinergic drugs (although not by vagotomy). Metoclopramide has been particularly effective in treating diabetic gastroparesis, delayed gastric emptying disorders, and esophageal reflux. The drug’s antagonism of serotonin has been useful in the treatment of migraine (32), although it failed to show efficacy in one placebo-controlled trial (11 ). Metoclopramide is usually well tolerated, although the high incidence of extrapyramidal side effects limits its use. Newer agents, such as the prokinetic agent cisapride (13,26), and the antiemetics domperidone, perphenizine, and odansetron (6,12,28,34), may be better tolerated. Metoclopramide may be administered by oral or intra venous routes. Oral doses are rapidly and completely ab- dosages (4). In serum, metoclopramide is about 30% protein-bound, primarily to albumin; this may contribute to toxicity in patients with hypoalbuminemic states (30). Due to its dopamine-blocking activity, metoclopramide can cause increased secretion of prolactin from the pituitary, leading to galactorrhea, amenorrhea, or impotence (8). It also elevates plasma aldosterone levels, possibly by 5-HT4 receptor antagonism (33). Tongue edema, or “blue tongue sign,” has been reported with metoclopramide (1).