Vomiting is a complex physiological response to expel harmful or irritating substances from the body. It's a defensive mechanism triggered by stimuli like poisons, microbial toxins, cytotoxic drugs, and mechanical abdominal distension. The process is centrally coordinated by the vomiting (or emetic) center located in the medulla of the brainstem. This area, rich in muscarinic M1, histamine H1, neurokinin 1 (NK1), and serotonin 5-HT3 receptors, coordinates the act of vomiting through interaction with cranial nerves and neural networks such as chemoreceptor trigger zone (CTZ) and the solitary tract nucleus (STN).

CTZ, a primary site of action for many emetic and antiemetic drugs, is crucial in initiating the vomiting reflex. It is located outside the blood-brain barrier, detecting stimuli in the blood and cerebrospinal fluid and signaling the emesis center to initiate vomiting. Another site, STN, is rich in receptors for enkephalin, histamine, acetylcholine, and serotonin receptors.

The vomiting center also receives signals from the vestibular apparatus in the inner ear, higher cortical centers, and afferent nerves from the gastrointestinal tract. The vestibular system, encompassing muscarinic and histamine receptors, is involved in motion sickness. The gastrointestinal tract's vagal and spinal afferent nerves, rich in 5-HT3 receptors, are activated by mucosal irritation due to chemotherapy, radiation, distention, or gastroenteritis. This leads to serotonin release and stimulates CTZ and the vomiting center, contributing to vomiting. Lastly, the central nervous system plays a role in emotional and stress-related vomiting.

Since several neurotransmitters such as serotonin, dopamine, histamine, acetylcholine, and substance P trigger the vomiting reflex by binding their respective receptors in the vomiting center or CTZ, they are valuable targets for various anti-emetic drugs.