A Novel Non-H₁, Non-H₂ Histamine Antagonist Protects against Cysteamine-induced Duodenal Ulcers in Rats

Abstract

A newly synthesized para-diphenylmethane derivative, N, N-dιethyl-2-[4-(phenylmethyl)phenoxy]ethanamine-HCl (DPPE), binds with high affinity to the microsomal anti-estrogen binding site (AEBS). Recent data suggest that the DPPE/AEBS binding site is closely related to a novel low-affinity, non-H₁, non-H₂ histamine site which may be associated with a calcium channel. We previously have shown that DPPE markedly reduces stress-induced and ethanol-induced gastric ulcers and attenuates gastric acid secretion. We now show that DPPE also profoundly reduces cysteamine-induced duodenal ulcers in rats.

Characterization of the Gastroprotective Effects of N, N-diethyl-2-[4-(phenylmethyl)phenoxy]-ethanamine Hydrochloride, a Non-H₁/Non- H₂ Histamine Antagonist

“…In particular, studies in both rat liver microsomes and rat brain cortical membranes indicate that [3H]-DPPE binding is not inhibited significantly by either pyrilamine (H| antagonist) or by cimetidine or ranitidine (H2 antagonists) [6], In tracheal smooth muscle, both pyrilamine and hydroxazine are 1,000 times more po tent than DPPE in blocking histamine-in duced contraction [10]. Because histamine and its antagonists are critical determinants of gastroduodenal ulcerogenesis and its treatment, respectively, and since the pres ence of lower-affinity histamine sites in ad dition to H2 sites on parietal cells has been suggested by others [11], we previously ex amined the effects of DPPE in several ani mal models of gastric function and ulcer ation [ 12,13], DPPE exhibited a unique pro file, markedly reducing both stress-induced and 100% ethanol-induced gastric ulcers as well as cysteamine-induced duodenal ulcers, and attenuating basal, H 2-agonist-stimulated and cholinergic-stimulated gastric acid se cretion. However, indomethacin pretreat ment abolished the protective effects of DPPE against gastric ulcer, leading us to sug gest that DPPE exerts its gastroprotection, at least in part, through prostaglandin-related mechanisms.…”