Control of transient lower esophageal sphincter relaxations and reflux by the GABAB agonist baclofen in normal subjects

Lidums, Ilmars; Lehmann, Anders; Checklin, Helen; Holloway, Richard L.

doi:10.1016/s0016-5085(00)70408-2

Cited by 304 publications

(249 citation statements)

References 32 publications

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“…It is possible for only baclofen to be effective in the treatment of acid reflux and it has been reported that baclofen, a gamma-aminobutyric acid B agonist, has been successful in decreasing the rate of TLESRs, as well as decreasing the number of acid reflux episodes in healthy subjects and patients with GERD (Lidums et al, 2000;Zhang et al, 2002). Baclofen has also been effective in reducing the symptoms associated with acid reflux and non-acid reflux in the postprandial period (Vela et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

The effects of nizatidine on transient lower esophageal sphincter relaxations (TLESRs) and acid reflux in healthy subjects

Iwakiri

Kawami

Sano

et al. 2011

J. Smooth Muscle Res.

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Background: A study in Japan has found that nizatidine (NIZ) is more effective than other histamine H2 receptor agonists (H2RAs) in treating reflux esophagitis (RE), although the NIZ group included a greater number of patients with severe RE. As there was no difference in the level of acid suppression among H2RAs, it is possible that NIZ has other effects on esophageal acid exposure (EAE) besides acid suppression. In this study, the effect of NIZ on transient lower esophageal sphincter relaxations (TLESRs) and acid reflux was evaluated in healthy subjects. Methods: In 10 healthy subjects, while in a sitting position, esophageal motility and a pH study were measured for 3 hours after a meal on 2 separate days at least 2 weeks apart. Participants received an oral dose of 150 mg of NIZ, 60 min before the meal on one day and a placebo on the other. Both studies were preceded by a week of treatment with either NIZ (150 mg, bid) or a placebo and the order of treatment was randomized. Results: Basal LES pressure in the NIZ group (14.1 mmHg, median) was significantly greater than that of the placebo group (8.5 mmHg). The rate of TLESRs in the NIZ group (22.0/3 h) for the postprandial 3-hour period was significantly less than that of the placebo group (16.5/3 h) and the rate of acid reflux during TLESRs (24.7%) and the EAE (0.2%) in the NIZ group for the postprandial 3-hour period was also significantly less than that of the placebo group (74.4% and 2.8%, respectively). Conclusion: NIZ significantly reduces acid reflux by inhibiting both the rate of TLESRs and acid reflux during TLESRs.

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Section: Discussionmentioning

confidence: 99%

The effects of nizatidine on transient lower esophageal sphincter relaxations (TLESRs) and acid reflux in healthy subjects

Iwakiri

Kawami

Sano

et al. 2011

J. Smooth Muscle Res.

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“…Considering transient lower esophageal sphincter relaxations account for the vast majority of reflux events [5], it is predictable that baclofen may be helpful for refractory GERC by the inhibition of both acid and nonacid reflux. The limited studies have shown that it decreased the frequency of transient lower esophageal sphincter relaxations by 40-60% and acid or non-acid reflux episodes by 43% [6][7][8]. Vela has illustrated that baclofen reduced the symptoms related to acid reflux by 72% and related non-acid reflux by 21% in a small cohort of patients with heartburn [9].…”

Section: Discussionmentioning

confidence: 99%

Successful Resolution of Refractory Chronic Cough Induced by Gastroesophageal Reflux With Treatment of Baclofen

Xu¹,

Qiu²,

Lv³

et al. 2012

Chest

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“…The first is based on the fact that baclofen has been proposed as an effective drug for the treatment of gastroesophageal reflux disease (GERD) by its ability to inhibit the intermittent relaxation of the LES. This is the main physiopathological mechanism that determines this dysfunction, thus reducing, with the therapeutic use of baclofen, the reflux of stomach content to the esophagus in humans (11,22,23,26,48) . There is no information about the effect of baclofen on the pylorus.…”

Section: Discussionmentioning

confidence: 99%

Effect of baclofen on liquid and solid gastric emptying in rats

Collares

Vinagre

2010

Arq. Gastroenterol.

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-Context -Gamma-aminobutyric acid (GABA) is a potent inhibitory neurotransmitter. There is evidence that GABA B receptors located in the dorsal complex and in afferent fibers of the vagus nerve participate in the control of gastrointestinal motility. Objectives -To assess the intracerebroventricularly (ICV) and intravenously (IV) effect of baclofen, a GABA B receptor agonist, on liquid and solid gastric emptying in rats. Methods -Adult male Wistar rats weighing 250-300 g (n = 6-8 animals) were used. Gastric emptying of liquid test meals labeled with phenol red was evaluated by the determination of percent gastric retention (%GR) 10 and 15 min after orogastric administration of saline and 10% glucose meals, respectively. Baclofen was injected ICV (1 and 2 mg/animal) through a tube implanted into the lateral ventricle of the brain and was injected IV (1 and 2 mg/kg) into a tail vein. The gastric emptying of liquid was determined 10 or 30 min after ICV and IV baclofen administration, respectively. The gastric emptying of the solid meal was assessed by the determination of percent gastric retention 2 h after the beginning of the ingestion of the habitual ratio by the animal, consumed over a period of 30 min. Baclofen was administered ICV (1 and 2 mg/animal) or IV (1 and 2 mg/kg) immediately after the end of the ingestion of the solid meal. The control groups received vehicle (sterile saline solution) ICV or IV.Results -The group of animals receiving baclofen ICV (2 mg/animal) presented a significantly lower (P<0.05, Tukey test) %GR (mean ± SEM) of the saline (18.1 ± 2.5%) compared to control (33.2 ± 2.2%). In the group receiving the drug IV, the gastric retention of the same test meal did not differ from control. ICV and IV administration of baclofen had no effect on the gastric emptying of the 10% glucose solution compared to control. ICV administration of 1 or 2 mg baclofen/animal significantly increased the gastric retention of the solid test meal (57.9 ± 6.5% and 66.6 ± 6.3%, respectively) compared to control (35.1 ± 4.4%). The same phenomenon was observed only with the IV dose of 2 mg/kg (71.9 ± 2.6%) compared to control (52.7 ± 2.8%). Conclusions -Baclofen administered: 1. ICV (2 mg/animal), but not IV, increased gastric emptying of a non-caloric isotonic liquid test meal (saline); 2. when administered ICV or IV, it had no effect of gastric emptying of a 10% glucose solution; 3) when administered ICV (1 and 2 mg/animal) and IV (2 mg/kg) it delayed the gastric emptying of the solid meal. HEADINGS -Gastric emptying. Baclofen. Rats.

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Control of transient lower esophageal sphincter relaxations and reflux by the GABAB agonist baclofen in normal subjects

Cited by 304 publications

References 32 publications

The effects of nizatidine on transient lower esophageal sphincter relaxations (TLESRs) and acid reflux in healthy subjects

The effects of nizatidine on transient lower esophageal sphincter relaxations (TLESRs) and acid reflux in healthy subjects

Successful Resolution of Refractory Chronic Cough Induced by Gastroesophageal Reflux With Treatment of Baclofen

Effect of baclofen on liquid and solid gastric emptying in rats

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