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

Furukawa, Takako; Nakayama, Hiroe; Kikuchi, Aya; Imazumi, Katsunori; Yamakuni, Hisashi; Sogabe, Hajime; Yamasaki, Sachiko; Takeshita, Koji; Matsuo, Makoto; Manda, Toshitaka; Uchida, Wataru

doi:10.1248/bpb.b12-01079

Cited by 3 publications

(1 citation statement)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Session 1 consisted of about 1‐h recordings of GMA and animal behaviors. In this session (control group), after a 15‐min baseline recording of GMA, hypodermic injection of apomorphine (0.1 mg/kg) solved into normal saline (0.01 mg/mL) was given. The GMA and animal behaviors were recorded throughout the entire experimental period for every 15 min.…”

Section: Methodsmentioning

confidence: 99%

Antiemesis effect and brain fMRI response of gastric electrical stimulation with different parameters in dogs

Lei

et al. 2014

Neurogastroenterology Motil

View full text Add to dashboard Cite

show abstract

Section: Methodsmentioning

confidence: 99%

Antiemesis effect and brain fMRI response of gastric electrical stimulation with different parameters in dogs

Lei

et al. 2014

Neurogastroenterology Motil

View full text Add to dashboard Cite

show abstract

Screening Methods for the Evaluation of Antiemetics

Maharani

2022

Introduction to Basics of Pharmacology and Toxicology

View full text Add to dashboard Cite

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

View full text Add to dashboard Cite

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 ...

show abstract

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

Cited by 3 publications

References 25 publications

Antiemesis effect and brain fMRI response of gastric electrical stimulation with different parameters in dogs

Antiemesis effect and brain fMRI response of gastric electrical stimulation with different parameters in dogs

Screening Methods for the Evaluation of Antiemetics

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

Contact Info

Product

Resources

About