Characterization of the gastroprotective effects of N,N-diethyl-2-[4-(phenylmethyl)phenoxy]-ethanamine hydrochloride, a non-H1/non-H2 histamine antagonist.

Abstract:

:N,N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine HCl (DPPE) is an antihistamine with a unique profile of activity in the stomach. It is antisecretory and blocks the formation of experimental cold/stress- and ethanol-induced gastric lesions, as well as cysteamine-induced duodenal ulcers in a fashion more potent than observed with histamine H2 antagonists such as cimetidine. We now demonstrate that the antiulcer effects of DPPE are associated with a dramatic (10-fold) rise in the stable prostacyclin hydration product 6-keto-prostaglandin F1 alpha in gastric secretion collected from conscious rats. Cyclooxygenase inhibitors such as acetylsalicylic acid, indomethacin and sodium meclofenamate abolish high-dose DPPE-induced gastroprotection, whereas sodium salicylate, a lipoxygenase inhibitor, does not. These data suggest that DPPE-induced gastroprotection is mediated, at least in part, through an increase in endogenous prostacyclin (prostaglandin I2) synthesis in the gastric mucosa. These data are not consistent with an effect of DPPE primarily at the H2 receptor, but are consistent with the recent suggestion that DPPE antagonizes histamine at HIC, an intracellular histamine site.

journal_name

Digestion

journal_title

Digestion

authors

Glavin GB,Gerrard JM

doi

10.1159/000200489

subject

Has Abstract

pub_date

1990-01-01 00:00:00

pages

143-8

issue

3

eissn

0012-2823

issn

1421-9867

journal_volume

47

pub_type

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