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

Objectives The purpose of this study was to determine whether rebamipide, an antistomach 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 h after stimulation with pilocarpine dissolved in physiological saline and intraperitoneally administered at 1 mg kg −1 . Diazepam ( DZP ) was administered intraperitoneally at a dose of 0.2 mg kg −1 twice daily for 7 days. Rebamipide was administered at 10, 20, 30, or 100 mg kg −1 concomitantly with DZP to determine its effect on hyposalivation. The effect of rebamipide on movement of intracellular calcium ([Ca 2+ ] i ) in isolated parotid acinar cells was analyzed using Fluo4, a fluorescent dye used to detect Ca 2+ . 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 −6 M) significantly suppressed carbachol (10 −7 M)‐induced increase in [Ca 2+ ] i . This inhibitory effect was ameliorated by combined use with rebamipide (5 × 10 −4 M). Conclusion This findings suggest that rebamipide weakens the downregulatory effect of DZP on salivary secretion by preventing DZP ‐induced suppression of increase in [Ca 2+ ] i .