(R)-Alpha-Methylhistamine Inhibits Ethanol-lnduced Gastric Lesions in the Rat: Involvement of Histamine H₃ Receptors?

Abstract

This study examined the gastroprotective effect of (R)-α-methylhistamine (MHA), a selective agonist of histamine H₃receptors. Gastric lesions were induced in the rat by administering absolute ethanol in a volume of 1 ml. Stomachs were removed 1 h later and lesions evaluated both macroscopically and histologically. MHA dose-dependently inhibited ethanol-induced lesions in the range 1-100 mg/kg both by the intragastric and intraperitoneal route. Histological findings indicated that the number of mucous granules in surface and neck cells was increased and the process of reepithelialization was rapidly promoted by MHA. Thioperamide, at 10 mg/kg, inhibited the protective effect of 10 but not of 100 mg/kg of MHA. Larger doses of thioperamide could not be tested because of an interaction with ethanol causing central nervous system effects. Famotidine and indomethacin pretreatment only partially counteracted the MHA effect. The results indicate that MHA is highly effective in preventing ethanol-induced lesions but the exact mechanism is still uncertain.

Ligands for histamine H3 receptors modulate cell proliferation and migration in rat oxyntic mucosa

“…We previously showed that the selective agonist of histamine H 3 receptors, (R)‐α‐methylhistamine ((R)α‐MeHA) (Arrang et al ., 1987), protects the gastric mucosa against acute damage from differently acting noxious agents in the rat (Morini et al ., 1995; 1997b). Its protective effect is reversed by the highly selective H 3 receptor antagonists clobenpropit and ciproxifan (Ligneau et al ., 1998; Morini et al ., 2000).…”

Histamine H3‐receptor antagonists inhibit gastroprotection by (R)‐α‐methylhistamine in the rat

“…(R)‐α‐methylhistamine [(R)α‐MeHa], a selective agonist of histamine H 3 receptors, exerts protective effects in various experimental models of gastric injury (Morini et al ., 1995; 1997). Based on the high degree of stereoselectivity of H 3 receptors (Arrang et al ., 1985), the failure of the S‐isomer of α‐methylhistamine to reduce total gastric lesions by absolute ethanol favours the hypothesis that H 3 receptors mediate gastroprotection by (R)α‐MeHA‐stimulation (Morini et al ., 1999).…”

Stereoselective Inhibition of Ethanol- Induced Gastric Lesions in the Rat by the H₃-Receptor Agonist (R)-α-Methylhistamine and Its (S)-Configured Isomer

“…(R)-·-methylhistamine protects the gastric mucosa from lesions induced by absolute ethanol in the rat [9]. It remains to be established whether or not this effect could be attributed to the interaction with histamine H 3 receptors.…”

“…Contrary to (R)-·-methylhistamine, the selective H 3 -receptor antagonists, thioperamide and, to a lesser extent, clobenpropit, cross the blood-brain barrier [10]. In rats, both compounds interact with ethanol to cause, with the only exception of their lower dose range, a marked central nervous system depression and the occurrence of coma [9]. Because of this interaction they could not be used to elucidate whether prevention of ethanol-induced gastric lesions by (R)-·-methylhistamine involves H 3 receptors.…”

“…[11]. (R)-·-methylhistamine was administered at the dose of 100 mg/kg as this had previously shown to exert the maximum protection of the gastric mucosa [9]. On a molar basis, the corresponding dose of (S)-·-methylhistamine was 55.44 mg/kg.…”