Mechanism of the Anti-Emetic Activity of 5-HT₃ Receptor Antagonists

Abstract

Ondansetron, a potent and highly selective 5-HT₃ receptor antagonist, prevents emesis following chemotherapy by antagonising the action of 5-hydroxytryptamine (5-HT) at 5-HT₃ receptors on vagal afferent neurones that innervate the gastrointestinal tract and 5-HT₃ receptors in the central vomiting system. Evidence suggests that chemotherapy induces the release of 5-HT from enterochromaffin cells in the small intestine. This stimulates vagal afferent nerves via 5-HT₃ receptors. Information is then relayed, via the vagus nerve, to the central vomiting system. 5-HT₃ receptors are also found in the hind-brain vomiting system including the area postrema (the site of the chemore-ceptor trigger zone for emesis). Therefore, following chemotherapy, 5-HT activates 5-HT₃ receptors at 2 sites to induce emesis. Clinical data showing that a single dose of ondansetron prevents acute emesis suggest that it is important to block the initiation of the emetic reflex. This may prevent the recruitment of central mechanisms involving 5-HT₃ receptors.

Effects of Grape Seed Proanthocyanidin on 5-Hydroxytryptamine3 Receptors in NCB-20 Neuroblastoma Cells

“…11,13,16) On the other hand, the 5-HT 3 receptors mediate emesis and pain, 27,28) and some antagonists of the 5-HT 3 receptors, like ondansetron, have been shown to prevent the development of pain and emesis. [29][30][31][32] In addition, some antiemetic drugs like metoclopramide have been reported to be potent antagonists of 5-HT 3 receptors. 21) Taken together, these findings suggest the possibility that proanthocyanidinmediated regulation of 5-HT 3 receptors is therapeutically relevant although we currently do not have direct evidence that proanthocyanidin can be used as a therapeutic agent for the alleviation of 5-HT 3 receptor-related clinical symptoms such as vomiting and pain.…”

Possible Involvement of 5-HT4 Receptors, in Addition to 5-HT3 Receptors, in the Emesis Induced by High-Dose Cisplatin in Suncus murinus

“…Activation of the 5-HT 3 receptors on EC cells induces the positive-feedback mechanism causing an increase of 5-HT release (15). Accordingly, 5-HT3-receptor antagonists inhibit the chemotherapy-induced emesis by the blockade of 5-HT3 receptors on EC cells as well as those on the vagus nerve endings (16). On the other hand, activation of 5-HT4 receptors is reported to either simulate or inhibit the 5-HT release in several animal species including ferret, rat, guinea pig, pig and human (17 -19).…”

Efeito de Hypericum caprifoliatum Cham. & Schltdl. (Guttiferae) sobre contrações em íleo isolado de cobaio induzidas por diferentes agonistas

“…Os subtipos de receptores serotoninérgicos majoritariamente encontrados no intestino são 5-HT 3 e 5-HT 4 (Tyers;Freedman, 1992, Hegde et al, 1995Degen et al, 2001;Costall;Naylor, 2004). As substâncias antagonistas 5-HT 3 , inibidoras da motilidade gástrica, são as mais relevantes na clínica, sendo que medicamentos como ondasetrona e granisetrona são utilizados no controle de náusea e vômito causados pela terapia anti-câncer (Costall;Naylor, 2004;Brandão, 2004;Herrstedt et al, 2005 …”