ANTICHOLINESTERASE ACTIVITY OF AND POSSIBLE ION‐CHANNEL BLOCK BY CIMETIDINE, RANITIDINE AND OXMETIDINE IN THE TOAD ISOLATED RECTUS ABDOMINIS MUSCLE

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Abstract
Responses of the toad isolated rectus abdominis muscle to cumulative doses of acetylcholine were recorded in the absence or presence of varying concentrations of cimetidine, ranitidine or oxmetidine. The corresponding cumulative log concentration-response curves for acetylcholine were then plotted for each antagonist studied. Cimetidine (5 mmol/l), ranitidine (1 mmol/l) and oxmetidine (0.02 mmol/l) potentiated the effect of acetylcholine by 4-fold, 2.6-fold and 1.3-fold, respectively. At higher concentrations all three histamine H2-receptor antagonists produced a concentration-dependent and non-parallel shift of the acetylcholine curve to the right of the corresponding control curve accompanied by a depression of the maximal response. The results provide further evidence that the H2-antagonists studied possess anticholinesterase activity and also suggest that the H2-antagonists may produce neuromuscular blockade by ion-channel block. The clinical implications of the results obtained are also discussed.

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