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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 gastric compliance in rats.Rats fasted for 18 h were orally administered indicated dose of aldioxa (mg kg−1) (a,c), acotiamide (100 mg kg−1) (a,c), allantoin (145 mg kg−1) (d), aluminium hydrate (Al(OH)3) (72 mg kg−1) (d), yohimbine (1 mg kg−1) (e), sucralfate (56 mg kg−1) (e) or vehicle (1% methylcellulose) (a,c–e). Rats were subjected to wrap restraint stress (WRS) for 1 h (b–e). Gastric compliance was measured one hour after the administration of each drug. Values are mean ± s.e.m. *P < 0.05; **P < 0.01 (Tukey test) (versus vehicle (a), versus control (b), versus WRS (c–e). Experiments were replicated at least two times.
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f7: Effect of aldioxa on gastric compliance in rats.Rats fasted for 18 h were orally administered indicated dose of aldioxa (mg kg−1) (a,c), acotiamide (100 mg kg−1) (a,c), allantoin (145 mg kg−1) (d), aluminium hydrate (Al(OH)3) (72 mg kg−1) (d), yohimbine (1 mg kg−1) (e), sucralfate (56 mg kg−1) (e) or vehicle (1% methylcellulose) (a,c–e). Rats were subjected to wrap restraint stress (WRS) for 1 h (b–e). Gastric compliance was measured one hour after the administration of each drug. Values are mean ± s.e.m. *P < 0.05; **P < 0.01 (Tukey test) (versus vehicle (a), versus control (b), versus WRS (c–e). Experiments were replicated at least two times.

Mentions: We next examined the effect of aldioxa on gastric compliance measured with a barostat apparatus (see Methods). As shown in Fig. 7a, increasing balloon pressure resulted in an increase in balloon volume. The pre-administration of acotiamide to animals potentiated this increase, as described previously in human18, showing that acotiamide increases gastric compliance. On the other hand, pre-administration of aldioxa did not significantly affect gastric compliance in control rats (Fig. 7a).


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 gastric compliance in rats.Rats fasted for 18 h were orally administered indicated dose of aldioxa (mg kg−1) (a,c), acotiamide (100 mg kg−1) (a,c), allantoin (145 mg kg−1) (d), aluminium hydrate (Al(OH)3) (72 mg kg−1) (d), yohimbine (1 mg kg−1) (e), sucralfate (56 mg kg−1) (e) or vehicle (1% methylcellulose) (a,c–e). Rats were subjected to wrap restraint stress (WRS) for 1 h (b–e). Gastric compliance was measured one hour after the administration of each drug. Values are mean ± s.e.m. *P < 0.05; **P < 0.01 (Tukey test) (versus vehicle (a), versus control (b), versus WRS (c–e). 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

f7: Effect of aldioxa on gastric compliance in rats.Rats fasted for 18 h were orally administered indicated dose of aldioxa (mg kg−1) (a,c), acotiamide (100 mg kg−1) (a,c), allantoin (145 mg kg−1) (d), aluminium hydrate (Al(OH)3) (72 mg kg−1) (d), yohimbine (1 mg kg−1) (e), sucralfate (56 mg kg−1) (e) or vehicle (1% methylcellulose) (a,c–e). Rats were subjected to wrap restraint stress (WRS) for 1 h (b–e). Gastric compliance was measured one hour after the administration of each drug. Values are mean ± s.e.m. *P < 0.05; **P < 0.01 (Tukey test) (versus vehicle (a), versus control (b), versus WRS (c–e). Experiments were replicated at least two times.
Mentions: We next examined the effect of aldioxa on gastric compliance measured with a barostat apparatus (see Methods). As shown in Fig. 7a, increasing balloon pressure resulted in an increase in balloon volume. The pre-administration of acotiamide to animals potentiated this increase, as described previously in human18, showing that acotiamide increases gastric compliance. On the other hand, pre-administration of aldioxa did not significantly affect gastric compliance in control rats (Fig. 7a).

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