A study in mice of benzodiazephine-anticholinergic interaction: protection against restraint-immersion and forced exertion-induced gastric mucosal erosion.
The effectiveness of benzodiazepines and anticholinergics administered alone or in combination in preventing restraint-immersion and forced exertion-induced gastric mucosal erosion was investigated in mice. The benzodiazepines used were diazepam and chlordiazepoxide HCI and the anticholinergics were propantheline bromide and clidinium bromide. The administratio of a benzodiazepine with an anticholinergic resulted in additive or supra-additive protective effects in both systems. In the restraint-immersion system, diazepam combined with propantheline bromide at a ratio of 1 to 13.7 yielded a 4.53-fold supra-additive effect. At ratios of 4.6 or 1.5 parts of propantheline bromide to 1 part of diazepam an additive effect was observed. One part of diazepam, when combined with 1.4 to 12.0 parts of clidinium bromide resulted in supra-additive effects of about 1.5-fold. The co-administration of chlordiazepoxide HCI and clidinium bromide in ratios of 2 to 1 or 2.5 to 1 resulted in supra-additive effects of 2.4- and 1.85-fold, respectively. At higher and lower ratios additive effects were demonstrated. In the forced exertion system, diazepam combined with either anticholinergic resulted in supra-additive effects of 2- to 3-fold which occurred at ratios of diazepam to the anticholinergic varying over an 8-fold range. The co-administration of 2 parts of chlordiazepoxide HCI and 1 part of clidinium bromide resulted in a 2.84-fold supra-additive effect in the forced exertion system. These results are discussed in relation to the use of benzodiazepine anticholinergic combinations in the treatment of human gastric and duodenal ulcer disease.
D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002707:Chlordiazepoxide / Q000627:therapeutic use; D003975:Diazepam / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004359:Drug Therapy, Combination; D005753:Gastric Mucosa / Q000473:pathology; D006471:Gastrointestinal Hemorrhage / Q000209:etiology; D007101:Immersion; D008297:Male; D051379:Mice; D010276:Parasympatholytics / Q000008:administration & dosage / Q000627:therapeutic use*; D005082:Physical Exertion; D011413:Propantheline / Q000627:therapeutic use; D011812:Quinuclidines / Q000627:therapeutic use; D013276:Stomach Ulcer / Q000209:etiology / Q000517:prevention & control*
D014151:Anti-Anxiety Agents; D010276:Parasympatholytics; D011812:Quinuclidines; D011413:Propantheline; D002707:Chlordiazepoxide; D003975:Diazepam