The tachykinin NK1 receptor antagonist GR205171 abolishes the retching activity of neurons comprising the central pattern generator for vomiting in dogs

Fukuda, Hiroyuki; Koga, Tomoshige; Furukawa, Naohiro; Nakamura, Emi; Shiroshita, Yasuteru

doi:10.1016/s0168-0102(98)00106-0

Cited by 25 publications

(33 citation statements)

References 33 publications

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“…The central pattern generator appears to be heavily innervated with NK 1 receptor-containing fibers, and information from pharmacological studies suggests that glutamatergic neurotransmissionviaAMPA/kainatereceptorsisalsoinvolved. 53,61,77,81 3. Dopamine: Synthesis, Storage, Release, Degradation, and Receptors Dopamine (DA) is a neurotransmitter in both the CNS and the periphery.…”

Section: Central Pattern Generator Areamentioning

confidence: 99%

“…92 Moderate NK 3 immunoreactivity has been observed in the rat NTS and DMNX. 208 The central pattern generator area, adjacent to the nucleus ambiguus, is heavily innervated by SP-containing afferents in many species, including the rat, 215 dog, 81 ferret, 53,216 human, 212 and least shrew. 217 Much of this data arose from basic anatomical research and was not directly correlated with vomiting.…”

Section: Dorsal Vagal Complexmentioning

confidence: 99%

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

2009

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Section: Central Pattern Generator Areamentioning

confidence: 99%

Section: Dorsal Vagal Complexmentioning

confidence: 99%

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

2009

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“…In addition, Zaman et al (75) reported that the NK 1 -receptor antagonist CP-99,994 had no significant effect on the c-fos expression in the NTS, although it inhibited emesis induced by the opioid receptor agonist loperamide. Taking the previous references into account (26,68,73,74,76), they suggested that NK 1 -receptor antagonists are likely to have a site of action "deeper" in the brainstem than the NTS (75). On the other hand, the 5-HT 3 -receptor antagonist granisetron abolished both the emetic effects of cisplatin and the c-fos expression in the NTS, because granisetron acted on 5-HT 3 receptors located on the vagus projection to the NTS (77).…”

Section: Substance P and Its Receptormentioning

confidence: 97%

“…Based on experiments using paralyzed decerebrate dogs with the NK 1 -receptor antagonist GR205171, injected either intravenous (25 -70 mg / kg) or microinjected into the fourth ventricle (1 m g/ ml, 30 m g), Fukuda et al (26,73,74) proposed that the sites of antiemetic action of the NK 1 -receptor antagonist exist on the neurons in the "afferent relay station". This station is situated between the medial NTS and the central pattern generator for vomiting (26).…”

Section: Substance P and Its Receptormentioning

confidence: 99%

Roles of Substance P and NK1 Receptor in the Brainstem in the Development of Emesis

2003

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Abstract. The emetic response is primarily a protective reflex occurring in a wide variety of vertebrates in response to the ingestion of toxic compounds. The role of the nuclei in the brainstem, including the area postrema, nucleus tractus solitarius, the dorsal motor nucleus of the vagus, and the central pattern generator for vomiting, as well as the involvement of the abdominal visceral innervation relevant to the emetic reflex, have all been discussed by many researchers. The introduction of serotonin 5-HT 3 -receptor antagonists into clinical practice allowed for a dramatic improvement in the management of vomiting. However, vomiting still remains a significant problem. The mechanism of the emetic response is even more complicated than was first thought. This review attempts to bring together some of the evidence suggesting the roles of substance P and its receptor, neurokinin NK 1 receptor, in the brainstem nuclei in the development of emesis. Accordingly, NK 1 -receptor antagonists might represent novel drugs for the management of major types of emesis.

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“…In a more recent investigation in decerebrate dogs, the NK-1 receptor antagonist was shown to inhibit firing 5-HT 1D receptor agonists such as sumatriptan and zolmitriptan. In addition to amelioration of the headache and in the brainstem region which generates the neural firing patterns necessary for retching and vomiting [54].…”

Section: Neurokinin Antagonists For Chemotherapy-induced Emesismentioning

confidence: 99%

Novel Approaches to the Treatment of Nausea and Vomiting

Ladabaum

Hasler²

1999

Dig Dis

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Nausea and vomiting are debilitating symptoms complicating many clinical conditions. Conventional antiemetic agents act as muscarinic, histamine, and dopamine receptor antagonists in the central nervous system. In a retrospective analysis, tricyclic antidepressant drugs demonstrated efficacy in long-term treatment of functional nausea. Some cases of vomiting result from impaired gastrointestinal motor activity. Agents which act on gastric serotonin (5-HT₄), dopamine, and motilin receptors accelerate gastric emptying and relieve symptoms in gastroparesis. Recent investigations suggest that some patients with refractory gastroparesis may benefit from gastric electrical pacing. The treatment of acute chemotherapy-induced emesis was revolutionized by 5-HT₃ receptor antagonists; however, these agents are less efficacious in delayed vomiting. Neurokinin (NK-1) receptor antagonists show promise in treating delayed chemotherapy-evoked emesis. Furthermore, animal studies indicate a broad spectrum of action for NK-1 antagonists in treating diverse causes of nausea and vomiting. The cyclic vomiting syndrome is characterized by discrete episodes of relentless vomiting separated by asymptomatic intervals and is associated with migraine headaches. Antimigraine therapies including the 5-HT_1D receptor agonists sumatriptan reduce the severity of cyclic vomiting attacks. Investigations into these and other novel treatments may provide important advances in the care of difficult cases of nausea and vomiting resulting from disparate illnesses.

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The tachykinin NK1 receptor antagonist GR205171 abolishes the retching activity of neurons comprising the central pattern generator for vomiting in dogs

Cited by 25 publications

References 33 publications

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

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

Roles of Substance P and NK1 Receptor in the Brainstem in the Development of Emesis

Novel Approaches to the Treatment of Nausea and Vomiting

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