Evidence for a Re-Evaluation of the Neurochemical and Anatomical Bases of Chemotherapy-Induced Vomiting

Darmani, Nissar A.; Ray, Andrew P.

doi:10.1021/cr900117p

Cited by 98 publications

(132 citation statements)

References 438 publications

(1,202 reference statements)

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“…In early studies it was shown that administration of substance P to dogs could induce emesis [3]. Multiple studies have suggested that substance P may be the most relevant neurotransmitter associated with delayed CINV [4]. …”

Section: Neuropharmacology Of Emesismentioning

confidence: 99%

Neuropharmacology and Management of Chemotherapy-Induced Nausea and Vomiting in Patients with Breast Cancer

et al. 2014

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Advances in our understanding of the pathophysiology of chemotherapy-induced nausea and vomiting (CINV), the identification of patient risk factors, and the development of new antiemetics have led to significant improvements in CINV prevention. With the correct use of antiemetic drugs, CINV can be prevented in the majority of patients. Extensive clinical data have been considered in the development of antiemetic treatment recommendations by reliable institutions such as the Multinational Association of Supportive Care in Cancer, the European Society of Medical Oncology and the American Society for Clinical Oncology. These guidelines are intended to enable physicians to incorporate the latest clinical research into their daily practice, considering CINV prevention as part of an optimal patient-centered approach to cancer management. Yet despite the availability of these guidelines, there is emerging evidence that implementation of treatment recommendations is suboptimal. Recently, guideline committees gave special consideration to patient-related risk factors (young, females) contributing to the emetogenic potential for patients receiving anthracycline and cyclophosphamide-based chemotherapy. As women with breast cancer represent a particularly challenging population regarding emesis control, it is especially important that treatment recommendations are followed. This review focuses on the content of the current antiemetic guidelines, addressing the importance of how these are intended to be implemented in routine clinical practice.

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Section: Neuropharmacology Of Emesismentioning

confidence: 99%

Neuropharmacology and Management of Chemotherapy-Induced Nausea and Vomiting in Patients with Breast Cancer

et al. 2014

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“…22,24) The dorsal vagal complex, which includes the area postrema (AP), nucleus tractus solitarii (NTS) and dorsal motor nucleus of the vagus nerve (DMN), and the central pattern generator area in the brainstem have been proposed as key mediators of the emetic reflex, and are known to be heavily innervated by NK 1 receptor-expressing fibers. 5,18,19) Various emetic stimuli, including cisplatin and apomorphine, increase the neuronal activity of this area in various species. [25][26][27] Furthermore, Darmani et al recently reported that cisplatin causes an over-expression of NK 1 receptor proteins in the brainstem, and that this over-expression is closely associated with the peak immediate-and delayed-phase vomiting frequencies in least shrew (Cryptotis parva).…”

Section: Apomorphine-induced Emetic Responsesmentioning

confidence: 99%

“…[15][16][17] Two key mediators of the emetic reflex, the dorsal vagal complex and the central pattern generator area, have been shown to be heavily innervated by NK 1 receptor-expressing fibers. 5,18,19) Recently we have reported the pharmacological properties of a novel NK 1 1 receptor antagonist that efficiently crosses the blood-brain barrier. 20) In the present study, we investigated the antiemetic efficacy of FK886 against two well-established dog emesis models, cisplatin-induced and apomorphineinduced emesis.…”

mentioning

confidence: 99%

Antiemetic Effects of a Potent and Selective Neurokinin-1 Receptor Antagonist, FK886, on Cisplatin- and Apomorphine-Induced Emesis in Dogs

Furukawa

Nakayama

Kikuchi

et al. 2013

Biological & Pharmaceutical Bulletin

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showed rapid onset of antiemetic activity after oral administration. At doses of 0.32 mg/kg or more, a pretreatment time of 0.5 h was sufficient for complete inhibition of apomorphine-induced emetic responses. This fast onset after oral administration was supported by pharmacokinetic data, which demonstrated plasma levels of FK886 after oral administration reached levels similar to those 30 min after intravenous administration. These results suggest that FK886 has excellent antiemetic properties in dogs, and that its rapid-onset and long-lasting properties might make it a promising antiemetic agent.

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“…Both the dorsal vagal complex, which includes the area postrema (AP), nucleus tractus solitarii (NTS) and dorsal motor nucleus of the vagus nerve (DMN), and the central pattern generator area in the brainstem have been proposed as key mediators of the emetic reflex, and are known to be heavily innervated by NK 1 receptor-expressing fibers. 12,13) Various emetic stimuli have been reported to increase the neuronal activity of this area in various species. [14][15][16] In particular, cisplatin causes an over-expression of NK 1 receptor proteins in the brainstem, which is closely associated with the peak acute-and delayed-phase vomiting frequencies in least shrews (Cryptotis parva).…”

mentioning

confidence: 99%

Antiemetic Effect of a Potent and Selective Neurokinin-1 Receptor Antagonist, FK886, on Cisplatin-Induced Acute and Delayed Emesis in Ferrets

Furukawa

Nakayama

Imazumi

et al. 2014

Biological & Pharmaceutical Bulletin

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The antiemetic effect of a potent and selective neurokinin-1 (NK 1 ) receptor antagonist, FK886 ([3,5-bis(trifluoromethyl) phenyl][(2R)-2-(3-hydroxy-4-methylbenzyl)-4-{2-[(2S)-2-(methoxymethyl)morpholin-4-yl]ethyl}piperazin-1-yl] methanone dihydrochloride), on cisplatin-induced acute and delayed emesis in ferrets was studied. Intravenous administration of FK886 dose-dependently inhibited cisplatin (10 mg/kg)-induced acute emesis with a minimum effective dose (MED) of 0.32 mg/kg. In the same study, oral FK886 administered 8 h prior to cisplatin also dose-dependently inhibited the acute emesis during the 4-h observation period with an MED of 3.2 mg/kg. Further, when given by repeated oral administration of ≥1.6 mg/kg at 12-h intervals, the first dose being administered 1 min before cisplatin, FK886 significantly decreased the number of emetic responses in cisplatin (5 mg/kg)-induced delayed emesis. In the same study, oral FK886 (3.2 mg/kg) repeatedly administrated at 12-h intervals, the first dose being administered 36 h post cisplatin, also significantly attenuated the delayed emesis. Pharmacokinetic data in ferrets showed that plasma FK886 reached a maximum concentration within 0.5 h of administration, suggesting rapid oral absorption. In addition, rapid brain penetration of FK886 was suggested by complete and near complete inhibition of GR73632-and copper sulfate-induced emesis, respectively, by low-dose intravenous FK886 administered shortly before the emetogens. These results suggest that FK886 is an orally available NK 1 receptor antagonist which is effective against both the acute and delayed emesis induced by cisplatin. Because of its therapeutic efficacy on the delayed emesis and rapid brain distribution after oral administration, FK886 may have potential as an antiemetic agent that can be used for interventional treatment of chemotherapy-induced delayed emesis.Key words FK886; neurokinin-1 antagonist; ferret emesis; cisplatin; GR73632; copper sulfate Nausea and vomiting are distressing symptoms that significantly detract from a patient's overall quality of life and their recovery during medical treatment. Nausea and vomiting both occur as symptoms of many diseases and as side effects of medical treatments, including cancer chemotherapy, radiotherapy, and general anesthesia in surgery. 1) Chemotherapy-induced nausea and vomiting (CINV) is perceived to be a major adverse effect of treatment by patients. 2) CINV may occur within hours of chemotherapy (acute phase) or be delayed until after the first 24 h, and then persist for several days (delayed phase). During the acute phase, chemotherapeutic agents induce serotonin (5-HT) release from enterochromaffin cells which stimulates local 5-HT 3 receptors on gastrointestinal vagal afferent nerves to initiate the vomiting reflex. [3][4][5] This may explain why 5-HT 3 antagonists have been shown to sufficiently control chemotherapy-induced acute emesis. [6][7][8] In contrast, 5-HT 3 antagonists are poorly effective against delayed emesis, 9,10) and the underlying ...

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Evidence for a Re-Evaluation of the Neurochemical and Anatomical Bases of Chemotherapy-Induced Vomiting

Cited by 98 publications

References 438 publications

Neuropharmacology and Management of Chemotherapy-Induced Nausea and Vomiting in Patients with Breast Cancer

Neuropharmacology and Management of Chemotherapy-Induced Nausea and Vomiting in Patients with Breast Cancer

Antiemetic Effects of a Potent and Selective Neurokinin-1 Receptor Antagonist, FK886, on Cisplatin- and Apomorphine-Induced Emesis in Dogs

Antiemetic Effect of a Potent and Selective Neurokinin-1 Receptor Antagonist, FK886, on Cisplatin-Induced Acute and Delayed Emesis in Ferrets

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