Emesis, antagonists area postrema

There are a few reports on possible sites of action of 5-HT3 antagonists. Low doses of zacopride administered directly into the fourth ventricle (i.c.v.) antagonized cisplatin (i.v.[-induced emesis in the cat [108]. A similar antagonism was demonstrated when routes of drug administration were interchanged. Similarly, GR 38032F, GR 65630 and MDL 72222, administered i.c.v. onto the area postrema at very low doses, antagonized cisplatin-induced... 

It can be concluded that direct evidence linking endogenous 5-HT to emesis is not convincing. On the other hand, selective effectiveness of 5-HT3 antagonists as antiemetic agents and presence of 5-HT3 receptors in the area postrema and vagus nerve do implicate 5-HT mechanisms. 

The 5-HT receptors function as ligand-gated ion channels and are expressed in the area postrema and solitary tract nucleus, where they couple to potent depolarizing responses that show rapid desensitization to continued 5-HT exposure. Actions of 5-HT at central 5-HT receptors can lead to emesis and antinociceptive actions, and 5-HT antagonists are beneficial in the management of chemotherapy-induced emesis (see Chapter 37). 

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