The new potent and selective histamine H2 receptor agonist amthamine as a tool to study gastric secretion.
The new histamine H2 receptor agonist amthamine, [2-amino-5-(2-aminoethyl)-4-methylthiazole], was tested for its activity on gastric acid secretion in different in vivo and in vitro experimental models. Amthamine induced a dose-related increase in acid secretion both in conscious cats with a gastric fistula (ED50 = 0.069 mumol/kg/h) and in anaesthetized rats with a lumen-perfused stomach (ED50 = 11.69 mumol/kg i.v.). In this last preparation the efficacy of amthamine was significantly higher than that of histamine and dimaprit. Amthamine was an effective secretagogue also in the rat isolated gastric fundus, behaving as a full agonist (EC50 = 18.9 mumol/l). In all the experimental models amthamine was more potent than dimaprit (from 3 to 10 fold) and approximately equipotent with histamine, and its effect was competitively antagonized by the histamine H2 receptor antagonists famotidine or ranitidine. Experiments with H1 and H3 receptor antagonists indicated that amthamine is devoid of stimulatory activity at H1 and H3 receptors. The present data indicate that amthamine is a full agonist at histamine H2 receptors and, being more effective and selective than the other compounds of the family, it may represent a good alternative to the other available histamine H2 receptor agonists for the study of gastric acid secretion.
Coruzzi
G
G
Institute of Pharmacology, University of Parma, Ospedale Maggiore, Italy.
Timmerman
H
H
Adami
M
M
Bertaccini
G
G
D000818:Animals; D002415:Cats; D004305:Dose-Response Relationship, Drug; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D011970:Receptors, Histamine H2 / Q000187:drug effects*; D013844:Thiazoles / Q000494:pharmacology*
D011970:Receptors, Histamine H2; D013844:Thiazoles; C076207:amthamine