The site of the anti-emetic action of tachykinin NK1 receptor antagonists may exist in the medullary area adjacent to the semicompact part of the nucleus ambiguus

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

doi:10.1016/s0006-8993(98)01324-9

Cited by 27 publications

(13 citation statements)

References 40 publications

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“…In this case, the microinjection of the dye into the dorsal part of the pontine tegmentum produced serial propulsive contractions of the descending colon and rectum, then blocked propulsive contractions in the reflex response to anal stimulation after bilateral microinjections. In a previous study, we showed that the microinjection of less than 5 l of aqueous solution produced no mechanical effect [11]. Therefore our present results with the microinjection of less than 1 l of PSB are not thought to be produced by mechanical effects.…”

Section: A Results Of the Experiments Using Psb As A Tool To Determinesupporting

confidence: 54%

“…The excitatory and blocking effects of PSB and its staining ability make it a useful tool for examining the functions of focal brain parts. [The Japanese Journal of Physiology 54: [61][62][63][64][65][66][67][68][69][70]2004] antiemetic action [11]. An injection of the antagonist into the medulla area corresponding to the central pattern generator for vomiting [13][14][15] produced no detectable effects.…”

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confidence: 99%

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Excitatory Neurotoxic Properties of Pontamine Sky Blue Make It a Useful Tool for Examining the Functions of Focal Brain Parts

Nagano

Ashidate

Yamamoto

et al. 2004

JJP

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Section: A Results Of the Experiments Using Psb As A Tool To Determinesupporting

confidence: 54%

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confidence: 99%

Excitatory Neurotoxic Properties of Pontamine Sky Blue Make It a Useful Tool for Examining the Functions of Focal Brain Parts

Nagano

Ashidate

Yamamoto

et al. 2004

JJP

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“…On the other hand, CP-122,721, a potent NK 1 -receptor antagonist, significantly prevented emesis evoked by all four of the above stimuli, as expected. Several studies suggest that the site of the antiemetic action of NK 1 -receptor antagonists is located in the brainstem known to be associated with the emetic reflex (11,12,16). Because diphenidol had negligible affinity for the NK 1 receptor, it is suggested that the hypothetical site of the anti-pica action of diphenidol by Takeda et al (8,9) is different from the site of NK 1 -receptor antagonists.…”

Section: Discussionmentioning

confidence: 99%

Diphenidol Has No Actual Broad Antiemetic Activity in Dogs and Ferrets

Nakayama¹,

Yamakuni²,

Nakayama³

et al. 2004

J Pharmacol Sci

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Abstract. Previous studies showed that diphenidol was effective on emetogens-induced pica, eating of non-nutritive substances, in rats, a model analogous to emesis in other species. We evaluated the actual antiemetic activity of diphenidol against four emetic stimuli in the dog and ferret, animals that possess an emetic reflex. In dogs, emetic responses to apomorphine were significantly prevented by diphenidol (3.2 mg / kg, i.v.), whereas diphenidol (3.2 mg / kg, i.v.´2) showed a weak inhibition to the vomiting evoked by cisplatin. In ferrets, diphenidol (10 mg / kg, i.p.) exhibited a weak antiemetic activity on the emesis induced by copper sulfate and had no activity on emesis by loperamide. On the other hand, CP-122,721, a NK 1 -receptor antagonist, significantly reduced the emetic episodes to all four stimuli. These results suggest that the prediction of antiemetic activity of compounds in animals lacking an emetic reflex does not always correspond with actual antiemetic activity.

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“…Patterns of nerve activity have been used to characterise emesis in paralysed, decerebrate preparations to define the correlates of emesis, i.e. retching and fictive expulsion (Fukuda & Koga, 1995;Miller et al 1996;Fukuda et al 1999).…”

Section: The Emetic Reflexmentioning

confidence: 99%

An Arterially Perfused Decerebrate Preparation of Suncus Murinus (House Musk Shrew) for the Study of Emesis and Swallowing

Smith

Paton

Andrews

2002

Experimental Physiology

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Arterially perfused, decerebrate preparations of the insectivore, Suncus murinus were made to determine whether the emetic reflex could be activated in such a preparation using a range of stimuli shown to be emetic in conscious or anaesthetised Suncus. Efferent phrenic and vagus nerve activities and electromyograms (EMGs) from the temporalis, abdominal oesophagus and trapezius muscles were recorded, as well as longitudinal shortening of the oesophagus and dorso‐ventral movements of the thorax. The preparations swallowed spontaneously every 0.6 to 6.5 min. The duration of a swallow was 3.1 ± 0.3 s (recorded as the time taken for the oesophagus to shorten and recover to its resting position) and the oesophagus shortened by 3.5 ± 0.4 mm during a swallow. The emetic reflex was activated by electrical stimulation (30 Hz, 10‐20 V, 0.2 ms pulse width, for 30 s) of abdominal vagal afferents (latency < 30 s) or by arterial perfusion with either 40 nM of the capsaicin analogue resiniferatoxin (latency 1.7 ± 0.6 min), 6 μM nicotine (latency 1.6 ± 0.1 min) or 1 μM of the phosphodiesterase IV inhibitor CP‐80,633 (latency 8.9 ± 3.9 min). These emetic stimuli produced somatic and visceral movements in Suncus preparations indicative of activation of the emetic reflex. There were pronounced contractions of the thorax that occurred simultaneously with oesophageal shortening and mouth opening, separated by thorax expansion and a burst of phrenic nerve activity. During emetic‐like episodes, oesophageal shortenings were only 0.84 ± 0.1 s in duration, faster than the duration of shortening observed during swallowing (cf. swallowing, 3.1 ± 0.3 s; P < 0.0001). The shortening of the oesophagus during emetic‐like episodes was 6.2 ± 0.4 mm, which was greater than the shortening seen during swallowing (cf. swallowing, 3.5 ± 0.4 mm; P < 0.0001). We conclude that the emetic reflex can be activated in our Suncus preparations and that this non‐sentient small adult animal model can now be used to study the neurophysiology and pharmacology of swallowing and emesis.

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The site of the anti-emetic action of tachykinin NK1 receptor antagonists may exist in the medullary area adjacent to the semicompact part of the nucleus ambiguus

Cited by 27 publications

References 40 publications

Excitatory Neurotoxic Properties of Pontamine Sky Blue Make It a Useful Tool for Examining the Functions of Focal Brain Parts

Excitatory Neurotoxic Properties of Pontamine Sky Blue Make It a Useful Tool for Examining the Functions of Focal Brain Parts

Diphenidol Has No Actual Broad Antiemetic Activity in Dogs and Ferrets

An Arterially Perfused Decerebrate Preparation of Suncus Murinus (House Musk Shrew) for the Study of Emesis and Swallowing

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