EXCITING INPUTS AND NEUROTRANSMITTER ROLE IN EMESIS OR REGULATION OF EMESIS

Proper pharmacological management of vomiting requires understanding of neuro transmitter  involvement in emesis.

1. The major afferent inputs to vomiting centre are routed through chemoreceptor trigger zone (CTZ; or areal prostema) which is located at the end of IV ventricle. Since CTZ lies outside of the BBB, it can feely monitor for toxic and emetogenic stimuli circulating in blood or CSF and can relay  this information to VC to trigger nausea and vomiting. The CTZ is rich in dopamine (D2), serotonin (5-HT3), muscarinic (M3), histamine (H1), opioid and NK1, receptors which could be the targets for existing and newer antiemetic drugs.

2. The vestibular apparatus generates impulses during motion sickness which reach VC mainly via cerebellum. Vestibular apparatus is rich in muscarinic (M1) and histaminic (H1) receptors.

 3.Vagal and splanchnic afferents in the GIT mucosa are rich in 5-HT3 receptor. Irritation of  GIT mucosa by irritants, chemotherapeutic agents, radiation therapy, endogenous toxin and poisons lead to a release of mucosal serotonin from enterochromaffin-like cells (ECL cells) which activate these 5-HT3 receptors. This propagates vagal afferent inputs to nucleus tractus solitarius (NTS) for onward transmission to VC. NTS is rich in histamine (H1), cholinergic (M1) and serotonin (5-HT3) receptors. 

4. Transmitter mediators in the cerebral cortex (higher centers) are poorly understood. However, cortical cannabinoid (CB1) receptors have been implicated. Muscarinic (M1) , histaminic (H1), serotonin (5-HT3) and Neurokinin-1 (NK1) receptors has a permissive role to play, as an excitatory neurotransmitter, in all sorts of emesis