Emetic neurotransmitters

Hamik A. Peroutka SJ. Differential interactions of traditional and novel anti-emetics with dopamine D2 and 5-hydroxytryptamine3 receptors. Cancer Chemotherapy Pharmacology. 1989 24(5) 307-10. Peroutka SJ, Snyder SH. Anti-emetics Neurotransmitter receptor binding predicts therapeutic actions. Lancet 1982 i 658-69. 

Established Emetic Neurotransmitters and More Novel Mediators of Vomiting.397... 

ESTABLISHED EMETIC NEUROTRANSMITTERS AND MORE NOVEL MEDIATORS OF VOMITING... 

Numerous neurotransmitter receptors are located in the vomiting center, CTZ, and GI tract. Examples of such receptors include cholinergic and histaminic, dopaminergic, opiate, serotonin, neurokinin (NK), and benzodiazepine receptors. Theoretically, chemotherapeutic agents, their metabolites, or other emetic compounds trigger the process of emesis through stimulation of one or more of these receptors. 

All of the opioid agonists produce some degree of tolerance and physical dependence. The biochemical mechanisms underlying tolerance and physical dependence are unclear. It is known, however, that intracellular mechanisms of tolerance to opioids include increases in calcium levels in the cells, increased production of cAMP, decreased potassium efflux, alterations in the phosphorylation of intracellular and intranuclear proteins, and the resultant return to normal levels of release of most neurotransmitters and neuromodulators. Tolerance to the analgesic effects of opioids occurs rapidly, especially when large doses of the drugs are used at short intervals. However, tolerance to the respiratory depressant and emetic effects of the opioids occurs more slowly. The miotic and constipative effects of the opioids rarely show tolerance. 

The 5-HT3 receptor is the only monoamine neurotransmitter receptor that functions as a lig-and-gated ion channel, controlling the flux of Na-i- and K+ ions. 5-HT3 receptors are located on parasympathetic nerve terminals in the gastrointestinal tract, and high densities are found in areas of the brain associated with the emetic response, such as the area postrema. The antiemetic effects of 5-HT3 antagonists, such as ondansetron, result from actions at these sites. 5-HT3 receptors in the dorsal horn of the spinal cord have been implicated in nociception and development of new 5-HT3 receptor-related compounds may have potential as non-opioid, non-addictive analgesics. 

FIGURE 18.4 Pharmacologist s view of emetic stimuli. Myriad signaling pathways lead from the periphery to the emetic center. Stimulants of these pathways are noted in italics. These pathways involve specific neurotransmitters and their receptors (bold text). Receptors are shown for dopamine, D acetylcholine (muscarinic), M histamine, H and 5-hydroxytryptamine, 5-HT. Some of these receptor types also may mediate signaling in the emetic center. This knowledge offers a rationale for current antiemetic therapy. 

Psychosis is caused by a dopamine (neurotransmitter) imbalance in the brain. Antipsychotic medications (dopamine antagonists) block the D2 dopamine receptors, reducing the psychotic symptoms. Some antipsychotic medications block the chemoreceptor trigger zone and vomiting (emetic) center, producing an antiemetic effect. Blocking dopamine causes the side effects of Parkinsonism (see 15.24 Parkinsonism Medication). Psychosis is treated with antipsychotic medications. Categories of antipsychotic are ... 

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