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Rebamipide, an anti‐ulcerative drug, inhibits induction of salivary dysfunction by benzodiazepines
Author(s) -
Ogane M,
Okubo M,
Yoshikawa M,
Shinomiya T,
Tsukagoshi E,
Kawaguchi M
Publication year - 2017
Publication title -
oral diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.953
H-Index - 87
eISSN - 1601-0825
pISSN - 1354-523X
DOI - 10.1111/odi.12642
Subject(s) - rebamipide , pilocarpine , saliva , carbachol , pharmacology , chemistry , stimulation , medicine , endocrinology , anesthesia , psychiatry , epilepsy
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 .