Prevention by (R)-alpha-methylhistamine of ethanol-induced gastric mucosal lesions in rats: importance of adherent mucus gel layer.

The ability of (R)-alpha-methylhistamine, the selective agonist of histamine H3 receptors, to reduce ethanol-induced gastric damage was examined in the rat. (R)-alpha-methylhistamine (1-100 mg/kg intragastrically) caused a dose-related reduction in the amount of damage produced by ethanol. This protective effect was not shared by the S enantiomer of alpha-methylhistamine. Thioperamide, selective H3 receptor antagonist, inhibited the protective effect of 10 but not 100 mg/kg of (R)-alpha-methylhistamine. Pretreatment with (R)-alpha-methylhistamine, 100 mg/kg i.g., resulted in a significant increase in the thickness of adherent mucus gel layer, which may contribute to the protective action of the compound.