anti-emetic D2-antagonists

D2 antagonists in GI

One class of drugs that is used to control motility in the gastrointestinal tract are The D2-antagonists. These drugs (such as metoclopramide and domperidone) block inhibitory D2 receptors on myenteric neurons, thereby increasing the release of acetylcholine from nerve terminals. This increase in acetylcholine can stimulate muscarinic-3 receptors, and increase muscular contractions. Both these drugs antagonise the D2 receptors located in the GI tract and thus increase gastric emptying, making them useful for the treatment of diabetic gastroparesis and gastro-oesophageal reflux.

Metoclopramide and domperidone also antagonise D2 receptors in the chemoreceptor trigger zone (CTZ), thereby decreasing emesis. However, domperidone does not readily cross the blood-brain barrier (BBB) and thus rarely causes extrapyramidal side effects. (note that the CTZ is in a part of the brain that is not protected by the BBB). In contrast to domperidone, which has almost pure D2 antagonist activity, metoclompramide also activates 5-HT4 receptors (see 5-HT4 agonists).


D2 antagonists have the most clinical relevance in:


The antiemetic effect of D2-antagonists is mainly due to