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Drug effects on gastric secretion and stress gastric hemorrhage in the rat

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The development of a simple, rapid technic for placing drugs into the rat lateral cerebral ventricle permitted comparison of intravenous and intracerebroventricular drug administration on gastric acid secretion and cold-plus-restraint (stress) induced gastric hemorrhage. Intravenous effective dose50's (micrograms) to reduce titratable acid output in 2-hr pylorus-ligated rats were: clonidine 1.0; atropine methylbromide 1.2; atropine sulfate 2.7; chlorpromazine 20.5; imipramine 397.0; morphine 837.7; and chlordiazepoxide 3419. The intravenous ED50's for inhibition of stress-induced gastric hemorrhage were (micrograms): atropine methylbromide 64.0; atropine sulfate 902.4; clonidine >4.0; chlorpromazine >256; morphine >256; chlordiazepoxide >2048; and imipramine >256. Intracerebroventricular administration of the drugs produced a different ranking of activity for inhibition of titratable acid output (ED50 in micrograms); atropine methylbromide 0.1; atropine sulfate 0.5; clonidine 3.7; morphine 5.5; chlorpromazine 99.2; chlordiazepoxide >1024; and imipramine >4096. However, the order of activity for intracerebroventricular inhibition of stress-induced gastric hemorrhage was similar to the intravenous route in that atropine methylbromide was most active, 7.8 μg, followed by atropine sulfate, 54.8 μg, and no ED50's were obtainable for the other drugs tested. This study indicated that central nervous system control areas for gastric secretion in the rat were located in structures bordering the cerebral ventricles but that secretion inhibiting dose of drug placed in this area did not reduce the incidence of stress-induced gastric hemorrhage.

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Brodie, D.A., Lotti, V.J. & Bauer, B.G. Drug effects on gastric secretion and stress gastric hemorrhage in the rat. Digest Dis Sci 15, 111–120 (1970).

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