5HT3 receptors

Maricq, A. V., Peterson, A. S., Brake, A. J., Myers, R. M., and Julius, D. (1991). Primary structure and function expression of the 5HT3 receptor, a serotonin-gated ion channel. Science 254 432-437. 

Yan D, Schulte MK, Bloom KE, While MM. 1999. Structural features of the ligand-binding domain of the serotonin 5HT3 receptor. J Biol Chem 274 5537-5541. 

Serotonin causes positive inotropic and chronotropic effects by interacting with both 51 ITj and 5HT3 receptors. 

Ondansetron, granisetron, topisetron, and batanopride are antagonists of the 5HT3 receptor, and are considered effective in controlling cancer-chemotherapy-induced emesis. Clozapine, an effective antipsychotic agent (neuroleptics) with little or no extrapyramidal... 

Morales M, Battenberg E, Bloom FE (1998) Distribution of neurons expressing immunoreactivity for the 5HT3 receptor subtype in the rat brain and spinal cord. J Comp Neurol 402 385 101 Morita H, Crone C, Christenhuis D, Petersen NT, Nielsen JB (2001) Modulation of presynaptic inhibition and disynaptic reciprocal la inhibition during voluntary movement in spasticity. Brain... 

Morales M, De Battenberg E, Bloom FE. Distribution of neurons expressing immunoreactivity for the 5HT3 receptor subtype in the rat brain and spinal cord. J Comp Neurol 1998 402 385-401. 

Pick H, Preuss AK, Mayer M, Wohland T, Hovius R, Vogel H. Monitoring expression and clustering of the ionotropic 5HT3 receptor in plasma membranes of live biological cells. Biochemistry 2003 42(4) 877-884. 

Ondansetron is one of a group of 5HT3-receptor antagonists currently available in the UK, which also includes granisetron, tropisetron, dolasetron and palonosetron. Dexamethasone is a corticosteroid. Ranitidine is a histamine-2 (H2)-receptor antagonist. 

Prophylactic administration of antiemetics is essential in any patient receiving FOLFOX chemotherapy. The combination of oxaliplatin and 5-fluorouracil results in a moderate level of emetogenicity and requires the administration of 5HT3-receptor antagonists and corticosteroid treatment, generally with a dopamine antagonist such as metoclopramide or domperidone. Severe manifestations may have to be managed by delay and/or dose modification of the patient s next cycle of chemotherapy. 

One of the major side-effects of cytotoxic chemotherapy is nausea and vomiting. It is essential therefore to control this with prophylactic antiemetic therapy. A number of agents are currently available and are effective at controlling chemotherapy-induced emesis. The most potent of these are 5HT3-receptor antagonists that include ondansetron, granisetron and palonosetron. 

The use of cytotoxic drugs with a high level of emetogenicity requires the prophylactic administration of a combination of a 5HT3-receptor antagonist and a corticosteroid to prevent the onset of acute nausea and vomiting (i.e. within the first 24 hours). 

There is little evidence supporting the use of 5HT3-receptor antagonists beyond the first 24 hours, and corticosteroids appear to be the most effective component of antiemetic regimens used to prevent delayed nausea and vomiting (American Society of Clinical Oncology et ah, 2006). 

Tropisetron is marketed outside the U.S. as a 5HT3 receptor antagonist for nausea, but it has a7-nicotinic agonist effects in the same concentration range. Tropisetron normalizes P50 inhibition in schizophrenics, with the effect primarily occurring in the nonsmoking subjects (Koike et al., 2005). 

---