Action of histamine and of different synthetic H2 receptor stimulants on the isolated gastric fundus of the guinea pig

Two series of compounds were studied for their stimulatory activity on acid secretion from the guinea pig gastric fundus. The first was represented by histamine and histamine methyl derivatives; the second by dimaprit (a specific stimulant of the H2 receptors) and dimaprit synthetic analogues derived from minor changes in the original molecule. Compounds in the first series were approximately equiactive in terms of threshold stimulant doses and of peak acid output but differed in maximal acid output: in fact methyl derivatives showed a longer lasting effect with a consequently higher stimulation of acid secretion in comparison to the parent substance. In the series of dimaprit and related analogues only the prototype, dimaprit, showed a good activity both in terms of threshold stimulant dose and maximal response. All the dimaprit-like compounds examined showed a very poor, if any, activity. Results are in agreement with data obtained in preliminary experiments using different preparations (estrus rat uterus, guinea pig in situ gall bladder) and suggest that the dimaprit molecule possesses the crucial chemical requirements to stimulate H2 receptors.