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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 clonidine-induced delayed gastric emptying.Mice fasted for 18 h were orally administered indicated dose (a) or 200 mg kg−1 (b,c) of aldioxa, indicated dose of cisapride (a) or vehicle (1% methylcellulose) (a–c). Fifty-five (a) or forty-five (b,c) minutes after each drug administration, delayed gastric emptying was induced by the subcutaneous administration of clonidine (100 (a) or 30 (b,c) μg kg−1). Control mice were subcutaneously administered saline (a–c). Gastric emptying was measured using the phenol red method (a) or the [13C]-labeled acetic acid breath test (b,c) and gastric emptying (a), Δ13CO2 (%) (b) and T1/2 (c) were calculated as described in the Methods. Values are mean ± s.e.m. *P < 0.05; **P < 0.01 (Tukey test). Experiments were replicated at least two times.
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f1: Effect of aldioxa on clonidine-induced delayed gastric emptying.Mice fasted for 18 h were orally administered indicated dose (a) or 200 mg kg−1 (b,c) of aldioxa, indicated dose of cisapride (a) or vehicle (1% methylcellulose) (a–c). Fifty-five (a) or forty-five (b,c) minutes after each drug administration, delayed gastric emptying was induced by the subcutaneous administration of clonidine (100 (a) or 30 (b,c) μg kg−1). Control mice were subcutaneously administered saline (a–c). Gastric emptying was measured using the phenol red method (a) or the [13C]-labeled acetic acid breath test (b,c) and gastric emptying (a), Δ13CO2 (%) (b) and T1/2 (c) were calculated as described in the Methods. Values are mean ± s.e.m. *P < 0.05; **P < 0.01 (Tukey test). Experiments were replicated at least two times.

Mentions: To begin with, we examined the effect of oral administration of aldioxa on clonidine-induced delayed gastric emptying. As shown in Fig. 1a, administration of clonidine delayed gastric emptying, and oral pre-administration of aldioxa partially restored the gastric emptying in a dose-dependent manner. The significant restoration was observed at both 200 and 670 mg kg−1 and the extent of restoration was similar between these doses (Fig. 1a). Restorative activity was also observed in mice treated with cisapride (Fig. 1a) as described previously22.


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 clonidine-induced delayed gastric emptying.Mice fasted for 18 h were orally administered indicated dose (a) or 200 mg kg−1 (b,c) of aldioxa, indicated dose of cisapride (a) or vehicle (1% methylcellulose) (a–c). Fifty-five (a) or forty-five (b,c) minutes after each drug administration, delayed gastric emptying was induced by the subcutaneous administration of clonidine (100 (a) or 30 (b,c) μg kg−1). Control mice were subcutaneously administered saline (a–c). Gastric emptying was measured using the phenol red method (a) or the [13C]-labeled acetic acid breath test (b,c) and gastric emptying (a), Δ13CO2 (%) (b) and T1/2 (c) were calculated as described in the Methods. Values are mean ± s.e.m. *P < 0.05; **P < 0.01 (Tukey test). 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

f1: Effect of aldioxa on clonidine-induced delayed gastric emptying.Mice fasted for 18 h were orally administered indicated dose (a) or 200 mg kg−1 (b,c) of aldioxa, indicated dose of cisapride (a) or vehicle (1% methylcellulose) (a–c). Fifty-five (a) or forty-five (b,c) minutes after each drug administration, delayed gastric emptying was induced by the subcutaneous administration of clonidine (100 (a) or 30 (b,c) μg kg−1). Control mice were subcutaneously administered saline (a–c). Gastric emptying was measured using the phenol red method (a) or the [13C]-labeled acetic acid breath test (b,c) and gastric emptying (a), Δ13CO2 (%) (b) and T1/2 (c) were calculated as described in the Methods. Values are mean ± s.e.m. *P < 0.05; **P < 0.01 (Tukey test). Experiments were replicated at least two times.
Mentions: To begin with, we examined the effect of oral administration of aldioxa on clonidine-induced delayed gastric emptying. As shown in Fig. 1a, administration of clonidine delayed gastric emptying, and oral pre-administration of aldioxa partially restored the gastric emptying in a dose-dependent manner. The significant restoration was observed at both 200 and 670 mg kg−1 and the extent of restoration was similar between these doses (Fig. 1a). Restorative activity was also observed in mice treated with cisapride (Fig. 1a) as described previously22.

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