Inhibitory effects of GABAB receptor agonists on swallowing in the dog

Lehmann, Anders; Bremner-Danielsen, Marianne; Brändén, Lena; Kärrberg, Lillevi

doi:10.1016/s0014-2999(02)01907-6

Cited by 19 publications

(18 citation statements)

References 19 publications

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“…We therefore hypothesize that the reduction in swallows and in primary peristalsis represent a consequence of the lower amount of acid inside the oesophageal wall 10 with subsequent reduced stimulus for clearing motor mechanisms 17 rather than a primary effect of the drug itself. Nevertheless a possibility exists of a concomitant direct action by baclofen on spontaneous and evoked swallows, as demonstrated in animals, 18 and this possibility is reinforced by the lack of significant alterations in secondary peristalsis in our patients.…”

Section: Discussionsupporting

confidence: 56%

Effect of baclofen on oesophageal motility and transient lower oesophageal sphincter relaxations in GORD patients: a 48‐h manometric study

Grossi

Spezzaferro

Sacco

et al. 2008

Neurogastroenterology Motil

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Little is known about prolonged effect of baclofen on oesophageal and lower oesophageal sphincter (LOS) motility. We aimed at investigating the oesophageal motility in gastro-oesophageal reflux disease (GORD) patients 24 h before and after the administration of multiple doses of baclofen. Twenty-one GORD patients underwent a 48-h manometry recording the swallows, the oesophageal and the LOS motility. During the second 24-h period, patients received baclofen 10 mg or placebo four times per day in a double-blind randomized fashion. Baclofen increased the LOS basal tone in comparison with baseline (P = 0.02), with a concomitant reduction in the number of transient LOS relaxations (TLOSRs) (P = 0.01). Moreover, baclofen induced a decrease of the swallows (P = 0.02) and of primary oesophageal body waves (P = 0.04) with no changes in the amplitude. Multiple doses of baclofen determine a reduction in the number of TLOSRs and an increase in the LOS tone throughout the 24 h. The concomitant decreased number of swallows and of primary peristalsis could depend on the well-known lower amount of reflux episodes induced by the drug. The potential therapeutic effect of baclofen could be expressed not only postprandially, but also in the fasting state when reflux episodes are present as well.

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Section: Discussionsupporting

confidence: 56%

Effect of baclofen on oesophageal motility and transient lower oesophageal sphincter relaxations in GORD patients: a 48‐h manometric study

Grossi

Spezzaferro

Sacco

et al. 2008

Neurogastroenterology Motil

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“…Therefore, we predicted that baclofen would decrease the number of marker swallows in our experimental system and used it as positive control. However, the finding that baclofen did not affect the number of marker swallows was unexpected and inconsistent with the results of a previous study showing that baclofen causes swallowing disorder (11). Further analyses demonstrated that the marker often congested in the upper esophagus of the animals given baclofen at 1.5 mg / kg.…”

Section: Discussioncontrasting

confidence: 94%

“…In the dog model used in this study, swallowing reflex was elicited by injection of a contrast medium into the pharynx at the volume of 1 mL. This model might be more sensitive to induction of swallowing reflex since Lehmann et al reported that the volume of water required to induce swallowing in dogs is about 4.4 mL (11). Since the dogs used in this study were kept in lateral recumbency, gravity might not work well on movement of the marker toward the stomach.…”

Section: Discussionmentioning

confidence: 99%

Swallowing Disorder and Inhibition of Cough Reflex Induced by Atropine Sulfate in Conscious Dogs

et al. 2008

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Abstract. In this study, the effects of atropine sulfate (atropine) on swallowing and cough reflex were evaluated in the two experimental models in conscious dogs. To evaluate the effects of atropine on swallowing, 1 mL of marker (contrast medium) was injected into the pharynx under X-ray exposure to induce swallowing. Baclofen, used as a positive control, caused marker congestion in the upper esophagus. In our experimental model, atropine (0.02 and 0.1 mg / kg, i.v.) dose-dependently increased not only the number of marker congestions but also that of the swallows. In addition, atropine significantly shortened the onset of first swallowing. In the evaluation of atropine effects on electrically evoked cough reflex induced by two electrodes implanted into the trachea, atropine strongly inhibited the number of coughs at 0.01 or 0.05 mg / kg accompanied with 0.01 or 0.05 mg / kg per hour (i.v.), respectively. These findings indicate that atropine has the potential of causing aspiration pneumonia through induction of swallowing disorder and inhibition of the cough reflex.

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“…GABA B receptors were also described on vagal-afferent terminals in the medullary brain stem region, which is important in the integration of sensory information from the stomach and the pharynx. Baclofen reduces the rate of transient lower esophageal sphincter relaxations and the number of reflux episodes, in humans and animals, which attracted a great deal of attention (34, 60,146,181,193,196,318). GABA B compounds may therefore open new possibilities in the treatment of disorders such as gastroesophageal reflux disease (60,196).…”

Section: Gastrointestinal Diseasementioning

confidence: 99%

Molecular Structure and Physiological Functions of GABA_BReceptors

Bettler

Kaupmann

Mosbacher

et al. 2004

Physiological Reviews

804

720

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GABAB receptors are broadly expressed in the nervous system and have been implicated in a wide variety of neurological and psychiatric disorders. The cloning of the first GABAB receptor cDNAs in 1997 revived interest in these receptors and their potential as therapeutic targets. With the availability of molecular tools, rapid progress was made in our understanding of the GABAB system. This led to the surprising discovery that GABAB receptors need to assemble from distinct subunits to function and provided exciting new insights into the structure of G protein-coupled receptors (GPCRs) in general. As a consequence of this discovery, it is now widely accepted that GPCRs can exist as heterodimers. The cloning of GABAB receptors allowed some important questions in the field to be answered. It is now clear that molecular studies do not support the existence of pharmacologically distinct GABAB receptors, as predicted by work on native receptors. Advances were also made in clarifying the relationship between GABAB receptors and the receptors for γ-hydroxybutyrate, an emerging drug of abuse. There are now the first indications linking GABAB receptor polymorphisms to epilepsy. Significantly, the cloning of GABAB receptors enabled identification of the first allosteric GABAB receptor compounds, which is expected to broaden the spectrum of therapeutic applications. Here we review current concepts on the molecular composition and function of GABAB receptors and discuss ongoing drug-discovery efforts.

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Inhibitory effects of GABAB receptor agonists on swallowing in the dog

Cited by 19 publications

References 19 publications

Effect of baclofen on oesophageal motility and transient lower oesophageal sphincter relaxations in GORD patients: a 48‐h manometric study

Effect of baclofen on oesophageal motility and transient lower oesophageal sphincter relaxations in GORD patients: a 48‐h manometric study

Swallowing Disorder and Inhibition of Cough Reflex Induced by Atropine Sulfate in Conscious Dogs

Molecular Structure and Physiological Functions of GABA_BReceptors

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Inhibitory effects of GABAB receptor agonists on swallowing in the dog

Cited by 19 publications

References 19 publications

Effect of baclofen on oesophageal motility and transient lower oesophageal sphincter relaxations in GORD patients: a 48‐h manometric study

Effect of baclofen on oesophageal motility and transient lower oesophageal sphincter relaxations in GORD patients: a 48‐h manometric study

Swallowing Disorder and Inhibition of Cough Reflex Induced by Atropine Sulfate in Conscious Dogs

Molecular Structure and Physiological Functions of GABABReceptors

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Molecular Structure and Physiological Functions of GABA_BReceptors