Pharmacological aspects of anticancer drug-induced emesis with emphasis on serotonin release and vagal nerve activity

Minami, Masaru; Endô, Tôru; Hirafuji, Masahiko; Hamaue, Naoya; Liu, Yanxia; Hiroshige, Tsutomu; Nemoto, M.; Saito, Hideya; Yoshioka, Mitsuhiro

doi:10.1016/s0163-7258(03)00057-3

Cited by 117 publications

(95 citation statements)

References 142 publications

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“…This could be explained by the mechanism of cisplatininduced nausea and vomiting which is probably mostly mediated by the serotonin release in the gastrointestinal enterochromaffin cells and not in the central nervous system (34). Thus, the haplotype of ABCB1 which could theoretically increase the amount of ondansetron that crosses the blood -brain barrier did not show significant impact in the ondansetron response.…”

Section: Discussionmentioning

confidence: 97%

Association of ABCB1, 5-HT3B Receptor and CYP2D6 Genetic Polymorphisms with Ondansetron and Metoclopramide Antiemetic Response in Indonesian Cancer Patients Treated with Highly Emetogenic Chemotherapy

Perwitasari¹,

Wessels²,

Straaten³

et al. 2011

Japanese Journal of Clinical Oncology

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Objective: Suboptimal treatment of chemotherapy-induced nausea and vomiting and unsatisfactory response to antiemetic drugs cause impairment of cancer patient's daily functioning. This study was aimed to investigate the association of selected germline polymorphisms with ondansetron and metoclopramide response in Indonesian cancer patients treated with highly emetogenic chemotherapy. Methods: We enrolled 202 chemotherapy naïve patients treated with cisplatin at a dosage of !50 mg/m 2 as monotherapy or as combined chemotherapy. Ondansetron 8 mg and dexamethasone 8 mg intravenously were the standard antiemetic therapy for prevention of acute chemotherapy-induced nausea and vomiting. Metoclopramide 10 mg orally, three times per day as fixed prescription, was given until 5 days after chemotherapy to prevent delayed chemotherapy-induced nausea and vomiting. Primary and secondary outcomes were the occurrence of chemotherapy-induced nausea and vomiting in the acute and delayed phase. The following single-nucleotide polymorphisms were determined in ABCB1: rs1045642, rs2032582 and rs1128503; in 5-HT3B-R: rs45460698, rs4938058 and rs7943062; and in CYP2D6: rs16947 (CYP2D6*2), rs3892097 (CYP2D6*4) and rs1065852 (CYP2D6*10) using Taqman assays. Results: During the acute phase, 21.8 and 30.2% patients experienced Grade 3 and 4 nausea and vomiting, respectively, whereas 38.6% patients experienced nausea and/or vomiting in the delayed phase. Carriers of the CTG haplotype of the ABCB1 gene experienced Grade 3 and 4 chemotherapy-induced nausea and vomiting more often than other haplotypes in the delayed phase (P , 0.05). No associations were found with the 5-HT3B receptor haplotypes and CYP2D6-predicted phenotypes. Conclusions: Our study shows that in Indonesian cancer patients treated with highly cytostatic emetogenic, carriership of the CTG haplotype of the ABCB1 gene is related to an increased risk of delayed chemotherapy-induced nausea and vomiting.

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Section: Discussionmentioning

confidence: 97%

Association of ABCB1, 5-HT3B Receptor and CYP2D6 Genetic Polymorphisms with Ondansetron and Metoclopramide Antiemetic Response in Indonesian Cancer Patients Treated with Highly Emetogenic Chemotherapy

Perwitasari¹,

Wessels²,

Straaten³

et al. 2011

Japanese Journal of Clinical Oncology

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“…Furthermore, 5-HT release from Enterochromaffin (EC) cells can be prevented by antagonists of both 5-HT 3 receptors and LTCCs. 48,49 Moreover, human duodenal EC cell exposure to FPL 64176 not only increases intracellular Ca 2+ concentration but can also release 5-HT from these cells, 50 which is a Ca 2+ -dependent process. 51 These findings provide possible mechanisms via which blockers of both LTCCs and 5-HT 3 receptors can mutually pre- vent the biochemical and behavioral effects of their corresponding selective agonists, including the vomiting behavior.…”

Section: Cross-talk Between Ltccs and 5ht 3 Rsmentioning

confidence: 99%

Role of Calcium in Vomiting: Revelations from the Least Shrew Model of Emesis

Darmani

Zhong²

2015

Gastro Open J

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Citation-ATPase inhibitor) cause vomiting in the least shrew, whereas blockade of LTCC by corresponding antagonists (nifedipine or amlodipine) not only provide broad-spectrum antiemetic activity against diverse emetogens including agonists of 5-HT 3 (e.g. 5-HT or 2-Me-5-HT)-, NK 1 (GR73632)-, D 2 (apomorphine or quinpirole)-, and M 1 (McN-A343)-receptors, but can also potentiate the antiemetic efficacy of well-established antiemetic palonosetron against the non-specific emetogen, cisplatin. The transmission of emesis signals in the gastrointestinal tract and brainstem is crucially dependent on Ca 2+ channels in neurons. In this review, we will examine the current knowledge on the role of Ca 2+ channels and Ca 2+-dependent signaling pathways in the perception and modulation of emesis.

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“…1 Antiemetic activity is believed to involve both peripheral receptors and those in the CNS. [7][8][9] Several studies have also suggested that 5-HT3…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Pharmacological Evaluation of [¹¹C]Granisetron and [¹⁸F]Fluoropalonosetron as PET Probes for 5-HT₃ Receptor Imaging

Herde

Rüefli

et al. 2016

ACS Chem. Neurosci.

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Serotonin-gated ionotropic 5-HT3 receptors are the major pharmacological targets for antiemetic compounds. Furthermore, they have become a focus for the treatment of irritable bowel syndrome (IBS) and there is some evidence that pharmacological modulation of 5-HT3 receptors might alleviate symptoms of other neurological disorders. Highly selective, high-affinity antagonists, such as granisetron (Kytril®) and palonosetron (Aloxi®), belong to a family of drugs (the 'setrons') that are well established for clinical use. To enable us to better understand the actions of these drugs in vivo, we report the synthesis of 8-fluoropalonosetron (15)

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Pharmacological aspects of anticancer drug-induced emesis with emphasis on serotonin release and vagal nerve activity

Cited by 117 publications

References 142 publications

Association of ABCB1, 5-HT3B Receptor and CYP2D6 Genetic Polymorphisms with Ondansetron and Metoclopramide Antiemetic Response in Indonesian Cancer Patients Treated with Highly Emetogenic Chemotherapy

Association of ABCB1, 5-HT3B Receptor and CYP2D6 Genetic Polymorphisms with Ondansetron and Metoclopramide Antiemetic Response in Indonesian Cancer Patients Treated with Highly Emetogenic Chemotherapy

Role of Calcium in Vomiting: Revelations from the Least Shrew Model of Emesis

Synthesis and Pharmacological Evaluation of [¹¹C]Granisetron and [¹⁸F]Fluoropalonosetron as PET Probes for 5-HT₃ Receptor Imaging

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Pharmacological aspects of anticancer drug-induced emesis with emphasis on serotonin release and vagal nerve activity

Cited by 117 publications

References 142 publications

Association of ABCB1, 5-HT3B Receptor and CYP2D6 Genetic Polymorphisms with Ondansetron and Metoclopramide Antiemetic Response in Indonesian Cancer Patients Treated with Highly Emetogenic Chemotherapy

Association of ABCB1, 5-HT3B Receptor and CYP2D6 Genetic Polymorphisms with Ondansetron and Metoclopramide Antiemetic Response in Indonesian Cancer Patients Treated with Highly Emetogenic Chemotherapy

Role of Calcium in Vomiting: Revelations from the Least Shrew Model of Emesis

Synthesis and Pharmacological Evaluation of [11C]Granisetron and [18F]Fluoropalonosetron as PET Probes for 5-HT3 Receptor Imaging

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Synthesis and Pharmacological Evaluation of [¹¹C]Granisetron and [¹⁸F]Fluoropalonosetron as PET Probes for 5-HT₃ Receptor Imaging