Abstract
In 9 dogs, whose maximum gastric acid response to pentagastrin was evoked by 6 μg/kg, the total gastric secretion as well as the peak gastric secretion was enhanced by amodiaquine. The optimum dose of this antimalarial drug was 2 mg/kg, whereas 0.25 mg/kg were without effect and 3 mg/kg reduced already the augmentation of gastric secretion by this substance. The increase in acid output by amodiaquine was greater than that in volume. The total secretion was more enhanced than the peak secretion, which means a longer duration of the amodiaquine potentiated gastric secretion elicited by pentagastrin, than that without application of amodiaquine contrary to that stimulated by exogenous histamine.
Amodiaquine itself did not stimulate gastric acid secretion, in contrast to prostigmine and carbachol. Thus amodiaquine seemed not to enhance gastric secretion by a direct or indirect parasympathomimetic action. The question whether amodiaquine acted on gastric secretion in a specific way and not by parasympathomimetic effects, led to investigations in several exocrine glands. In salivary glands, amodiaquine did neither stimulate the secretion in all doses investigated nor did it enhance the pilocarpine and acetylcholine induced salivation with any significance and regularity. Also the pancreatic and biliary secretion was neither stimulated by amodiaquine nor was the secretin induced secretion of the pancreas and liver augmented by amodiaquine. Thus the enhancing effect of this drug on the histamine and pentagastrin stimulated gastric secretion was very likely specific for the gastric mucosa and not due to a parasympathomimetic action of the drug.
In contrast to the findings in various exocrine glands of the gastrointestinal tract, the arterial hypotension following the i.v. injection of acetylcholine was increased specifically by a preceeding i.v. injection of amodiaquine, whereas the equi-effective actions of histamine, serotonin and bradykinin as well as the hypertension by epinephrine and norepinephrine were not influenced by amodiaquine. This specific effect of the antimalarial drug very probably was not caused by an inhibition of the unspecific choline esterase in the blood.
Since in exocrine glands no evidence could be found for a parasympathomimetic action or other modes of action of amodiaquine, it seemed probable that amodiaquine potentiated the histamine and pentagastrin stimulated gastric secretion by an inhibition of histamine methyltransferase in vivo.
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Supported by grants from Deutsche Forschungsgemeinschaft (Lo 199/3) and E. Merck AG, Darmstadt.
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Troidl, H., Lorenz, W., Barth, H. et al. Augmentation of pentagastrin stimulated gastric secretion in the heidenhain pouch dog by amodiaquine: Inhibition of histamine methyltransferase in vivo?. Agents and Actions 3, 157–167 (1973). https://doi.org/10.1007/BF01965726
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DOI: https://doi.org/10.1007/BF01965726