Gastric secretory studies in humans with impromidine (SK&F 92676)—a specific histamine H2 receptor agonist
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Impromidine (SK&F 92676), a potent selective histamine H2-receptor agonist in animals has been studied in healthy male volunteers. Impromidine 10 micrograms kg-1h-1 i.v. produced near maximal acid secretion and cimetidine 2 mg kg-1h-1 inhibited this output by a mean of 65% in 5 subjects. The log dose-response curve to impromidine in 5 subjects was linear over the dose range 2.5--20 micrograms kg-1h-1. Cimetidine 0.5 mg kg-1h-1 caused a highly significant parallel shift of the dose-response curve, consistent with direct competitive antagonism. The gastric secretory responses to impromidine 10 micrograms kg-1h-1 i.v., histamine acid phosphate 40 micrograms kg-1h-1 i.v., and pentagastrin 6 micrograms kg-1h-1 i.v. were similar. Cardiovascular effects of impromidine were less marked than those due to histamine. Gastric secretory and cardiovascular effects of impromidine are dose dependent. No significant difference was seen in peak acid output between impromidine 10 micrograms kg-1 and pentagastrin 6 micrograms kg-1 whether injected intramuscularly or subcutaneously. Headache which accompanied infusion with histamine occurred less frequently with impromidine, and nausea and abdominal discomfort which occurred with pentagastrin did not occur with impromidine. Impromidine will be valuable in the study of gastric secretion and the role of histamine H2 receptors in other systems.
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