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Aldioxa improves delayed gastric emptying and impaired gastric compliance, pathophysiologic mechanisms of functional dyspepsia.

Asano T, Aida S, Suemasu S, Tahara K, Tanaka K, Mizushima T - Sci Rep (2015)

Bottom Line: Oral administration of aldioxa (dihydroxyaluminum allantoinate) partially improved clonidine- or restraint stress-induced delayed gastric emptying.Both aldioxa and allantoin inhibited clonidine binding to the α-2 adrenergic receptor, suggesting that antagonistic activity of the allantoin moiety of aldioxa on this receptor is involved in the restoration of gastric emptying activity.We propose that aldioxa is a candidate drug for FD, because its safety in humans has already been confirmed and its ameliorating effect on both of delayed gastric emptying and impaired gastric compliance are confirmed here.

View Article: PubMed Central - PubMed

Affiliation: Department of Drug Discovery and Development, Faculty of Pharmacy, Keio University, 1-5-30, Shibakoen, Minato-ku, Tokyo 105-8512, Japan.

ABSTRACT
Delayed gastric emptying and impaired gastric accommodation (decreased gastric compliance) play important roles in functional dyspepsia (FD). Here we screen for a clinically used drug with an ability to improve delayed gastric emptying in rats. Oral administration of aldioxa (dihydroxyaluminum allantoinate) partially improved clonidine- or restraint stress-induced delayed gastric emptying. Administration of allantoin, but not aluminium hydroxide, restored the gastric emptying. Both aldioxa and allantoin inhibited clonidine binding to the α-2 adrenergic receptor, suggesting that antagonistic activity of the allantoin moiety of aldioxa on this receptor is involved in the restoration of gastric emptying activity. Aldioxa or aluminium hydroxide but not allantoin restored gastric compliance with restraint stress, suggesting that aluminium hydroxide moiety is involved in this restoration. We propose that aldioxa is a candidate drug for FD, because its safety in humans has already been confirmed and its ameliorating effect on both of delayed gastric emptying and impaired gastric compliance are confirmed here.

No MeSH data available.


Related in: MedlinePlus

Effect of aldioxa on restraint stress-induced delayed gastric emptying and normal gastric emptying.Mice fasted for 18 h were orally administered aldioxa (200 mg kg−1) (a–d), mosapride (7.7 mg kg−1) (a–d), cisapride (5 mg kg−1) (d) or vehicle (1% methylcellulose) (a–d) and delayed gastric emptying was induced by restraint stress (RS) (a–c). One hour after the administration of each test compound, gastric emptying was measured using the phenol red method (a,d) or the [13C]-labeled acetic acid breath test (b,c) as described in the legend of Fig. 1. Values are mean ± s.e.m. *P < 0.05; **P < 0.01 (Tukey test). n.s., not significant. Experiments were replicated at least two times.
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f4: Effect of aldioxa on restraint stress-induced delayed gastric emptying and normal gastric emptying.Mice fasted for 18 h were orally administered aldioxa (200 mg kg−1) (a–d), mosapride (7.7 mg kg−1) (a–d), cisapride (5 mg kg−1) (d) or vehicle (1% methylcellulose) (a–d) and delayed gastric emptying was induced by restraint stress (RS) (a–c). One hour after the administration of each test compound, gastric emptying was measured using the phenol red method (a,d) or the [13C]-labeled acetic acid breath test (b,c) as described in the legend of Fig. 1. Values are mean ± s.e.m. *P < 0.05; **P < 0.01 (Tukey test). n.s., not significant. Experiments were replicated at least two times.

Mentions: Restraint stress-induced delayed gastric emptying has been used as an alternative animal model of FD28, prompting us to examine here the efficacy of aldioxa in this model. As shown in Fig. 4a, the phenol red method revealed that mice subjected to restraint stress showed delayed gastric emptying, which was partially suppressed by the pre-administration of aldioxa or mosapride to animals. Similar results were observed with the [13C]-labeled acetic acid breath test (Fig. 4b,c).


Aldioxa improves delayed gastric emptying and impaired gastric compliance, pathophysiologic mechanisms of functional dyspepsia.

Asano T, Aida S, Suemasu S, Tahara K, Tanaka K, Mizushima T - Sci Rep (2015)

Effect of aldioxa on restraint stress-induced delayed gastric emptying and normal gastric emptying.Mice fasted for 18 h were orally administered aldioxa (200 mg kg−1) (a–d), mosapride (7.7 mg kg−1) (a–d), cisapride (5 mg kg−1) (d) or vehicle (1% methylcellulose) (a–d) and delayed gastric emptying was induced by restraint stress (RS) (a–c). One hour after the administration of each test compound, gastric emptying was measured using the phenol red method (a,d) or the [13C]-labeled acetic acid breath test (b,c) as described in the legend of Fig. 1. Values are mean ± s.e.m. *P < 0.05; **P < 0.01 (Tukey test). n.s., not significant. Experiments were replicated at least two times.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4664916&req=5

f4: Effect of aldioxa on restraint stress-induced delayed gastric emptying and normal gastric emptying.Mice fasted for 18 h were orally administered aldioxa (200 mg kg−1) (a–d), mosapride (7.7 mg kg−1) (a–d), cisapride (5 mg kg−1) (d) or vehicle (1% methylcellulose) (a–d) and delayed gastric emptying was induced by restraint stress (RS) (a–c). One hour after the administration of each test compound, gastric emptying was measured using the phenol red method (a,d) or the [13C]-labeled acetic acid breath test (b,c) as described in the legend of Fig. 1. Values are mean ± s.e.m. *P < 0.05; **P < 0.01 (Tukey test). n.s., not significant. Experiments were replicated at least two times.
Mentions: Restraint stress-induced delayed gastric emptying has been used as an alternative animal model of FD28, prompting us to examine here the efficacy of aldioxa in this model. As shown in Fig. 4a, the phenol red method revealed that mice subjected to restraint stress showed delayed gastric emptying, which was partially suppressed by the pre-administration of aldioxa or mosapride to animals. Similar results were observed with the [13C]-labeled acetic acid breath test (Fig. 4b,c).

Bottom Line: Oral administration of aldioxa (dihydroxyaluminum allantoinate) partially improved clonidine- or restraint stress-induced delayed gastric emptying.Both aldioxa and allantoin inhibited clonidine binding to the α-2 adrenergic receptor, suggesting that antagonistic activity of the allantoin moiety of aldioxa on this receptor is involved in the restoration of gastric emptying activity.We propose that aldioxa is a candidate drug for FD, because its safety in humans has already been confirmed and its ameliorating effect on both of delayed gastric emptying and impaired gastric compliance are confirmed here.

View Article: PubMed Central - PubMed

Affiliation: Department of Drug Discovery and Development, Faculty of Pharmacy, Keio University, 1-5-30, Shibakoen, Minato-ku, Tokyo 105-8512, Japan.

ABSTRACT
Delayed gastric emptying and impaired gastric accommodation (decreased gastric compliance) play important roles in functional dyspepsia (FD). Here we screen for a clinically used drug with an ability to improve delayed gastric emptying in rats. Oral administration of aldioxa (dihydroxyaluminum allantoinate) partially improved clonidine- or restraint stress-induced delayed gastric emptying. Administration of allantoin, but not aluminium hydroxide, restored the gastric emptying. Both aldioxa and allantoin inhibited clonidine binding to the α-2 adrenergic receptor, suggesting that antagonistic activity of the allantoin moiety of aldioxa on this receptor is involved in the restoration of gastric emptying activity. Aldioxa or aluminium hydroxide but not allantoin restored gastric compliance with restraint stress, suggesting that aluminium hydroxide moiety is involved in this restoration. We propose that aldioxa is a candidate drug for FD, because its safety in humans has already been confirmed and its ameliorating effect on both of delayed gastric emptying and impaired gastric compliance are confirmed here.

No MeSH data available.


Related in: MedlinePlus