Mixed antisecretory and gastroprotective activities of a new H2-antagonist containing a nitric oxide-donor furoxan moiety.
The effect of a new histamine H2-receptor antagonist derived from the lamtidine molecule and containing a nitric oxide (NO)-donor furoxan moiety (derivative 1) was studied for its gastric antisecretory activity and for a possible gastroprotective effect, in comparison with the analog without the furoxan moiety (derivative 2). The H2-receptor antagonistic activity was also investigated in the isolated guinea pig papillary muscle. Derivative 1 was approximately 10 times less potent than derivative 2 at the H2-receptor level; conversely, it was about 10 times more effective as a gastroprotective agent against ethanol- and 0.6 N HCl-induced gastric lesions. The mechanism of the gastroprotection exerted by derivative 1 is probably connected with the release of NO, whose vasodilating action on gastric mucosa vessels is crucial. The combined antisecretory and gastroprotective activity of derivative 1 allows this compound to be considered as a prototype of a new class of antiulcer agents.
Sorba
G
G
Dipartimento di Scienza e Tecnologia del Farmaco, Università di Torino, Italy.
Gasco
A
A
Coruzzi
G
G
Adami
M
M
Pozzoli
C
C
Morini
G
G
Bertaccini
G
G
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D002492:Central Nervous System Depressants; D000431:Ethanol; D005753:Gastric Mucosa / Q000473:pathology; D006168:Guinea Pigs; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D010210:Papillary Muscles / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013276:Stomach Ulcer / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control
D000897:Anti-Ulcer Agents; D002492:Central Nervous System Depressants; D006635:Histamine H2 Antagonists; D009569:Nitric Oxide; D000431:Ethanol