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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 allantoin or aluminium hydrate on clonidine-induced delayed gastric emptying.Mice fasted for 18 h were orally administered aldioxa (200 mg kg−1), allantoin (145 mg kg−1), aluminium hydrate (Al(OH)3) (72 mg kg−1) or vehicle (1% methylcellulose). Clonidine-induced delayed gastric emptying was induced and measured using the phenol red method as described in the legend of Fig. 1. Values are mean ± s.e.m. *P < 0.05 (Tukey test). n.s., not significant. Experiments were replicated at least two times.
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f3: Effect of allantoin or aluminium hydrate on clonidine-induced delayed gastric emptying.Mice fasted for 18 h were orally administered aldioxa (200 mg kg−1), allantoin (145 mg kg−1), aluminium hydrate (Al(OH)3) (72 mg kg−1) or vehicle (1% methylcellulose). Clonidine-induced delayed gastric emptying was induced and measured using the phenol red method as described in the legend of Fig. 1. Values are mean ± s.e.m. *P < 0.05 (Tukey test). n.s., not significant. Experiments were replicated at least two times.

Mentions: We also separately examined the effect of allantoin or aluminium hydrate on clonidine-induced delayed gastric emptying. As shown in Fig. 3, allantoin but not aluminium hydrate partially improved clonidine-induced delayed gastric emptying at an equivalent dose to that of aldioxa (with respect to molecular number, 200 mg kg−1 of aldioxa corresponds to 145 or 72 mg kg−1 of allantoin or aluminium hydrate, respectively). The results in Figs 2 and 3 thus suggest that aldioxa achieves its stimulatory effect on gastric emptying independently of its gastroprotective effect, and that the allantoin moiety of aldioxa is important for improved emptying.


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 allantoin or aluminium hydrate on clonidine-induced delayed gastric emptying.Mice fasted for 18 h were orally administered aldioxa (200 mg kg−1), allantoin (145 mg kg−1), aluminium hydrate (Al(OH)3) (72 mg kg−1) or vehicle (1% methylcellulose). Clonidine-induced delayed gastric emptying was induced and measured using the phenol red method as described in the legend of Fig. 1. Values are mean ± s.e.m. *P < 0.05 (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

f3: Effect of allantoin or aluminium hydrate on clonidine-induced delayed gastric emptying.Mice fasted for 18 h were orally administered aldioxa (200 mg kg−1), allantoin (145 mg kg−1), aluminium hydrate (Al(OH)3) (72 mg kg−1) or vehicle (1% methylcellulose). Clonidine-induced delayed gastric emptying was induced and measured using the phenol red method as described in the legend of Fig. 1. Values are mean ± s.e.m. *P < 0.05 (Tukey test). n.s., not significant. Experiments were replicated at least two times.
Mentions: We also separately examined the effect of allantoin or aluminium hydrate on clonidine-induced delayed gastric emptying. As shown in Fig. 3, allantoin but not aluminium hydrate partially improved clonidine-induced delayed gastric emptying at an equivalent dose to that of aldioxa (with respect to molecular number, 200 mg kg−1 of aldioxa corresponds to 145 or 72 mg kg−1 of allantoin or aluminium hydrate, respectively). The results in Figs 2 and 3 thus suggest that aldioxa achieves its stimulatory effect on gastric emptying independently of its gastroprotective effect, and that the allantoin moiety of aldioxa is important for improved emptying.

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