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

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).

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 ([Ca²⁺ ]i) in isolated parotid acinar cells was analyzed using Fluo4, a fluorescent dye used to detect Ca²⁺ .

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 [Ca²⁺ ]i. This inhibitory effect was ameliorated by combined use with rebamipide (5 × 10^-4 M).

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