Rebamipide, an anti-ulcerative drug, inhibits induction of salivary dysfunction by benzodiazepines

Abstract

Objectives

The purpose of this study was to determine whether rebamipide, an anti-stomach ulcer agent, ameliorated benzodiazepine-induced hyposalivation in rat parotid gland (PG) and submandibular gland (SMG).

Methods

Saliva was collected from PG and SMG through a capillary cannula inserted into the parotid duct and sublingual papillae, respectively, every 15 min for 1 hr after stimulation with pilocarpine dissolved in physiological saline and intraperitoneally administered at 1 mg/kg. Diazepam (DZP) was administered intraperitoneally at a dose of 0.2 mg/kg twice daily for 7 days. Rebamipide was administered at 10, 20, 30, or 100 mg/kg concomitantly with DZP to determine its effect on hyposalivation. The effect of rebamipide on movement of intracellular calcium ([Ca²⁺]i) in isolated parotid acinar cells was analyzed by using Fluo4, a fluorescent dye used to detect Ca²⁺.

Results

Repetitive administration of DZP decreased salivary secretion in PG and SMG. This inhibitory effect was weakened by administration of rebamipide. Prior administration of DZP (10^-6M) significantly suppressed carbachol (10^-7M)-induced increase in [Ca²⁺]i. This　inhibitory effect was ameliorated by combined use with rebamipide (5 x 10^-4M).

Conclusion

The present findings suggest that rebamipide weakens the down-regulatory effect of DZP on salivary secretion by preventing DZP-induced suppression of increase in [Ca²⁺]i.

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