N-ALPHA-METHYLHISTAMINE INHIBITS INTESTINAL TRANSIT IN MICE BY CENTRAL HISTAMINE H-1 RECEPTOR ACTIVATION

The effects of (R)alpha-methylhistamine and N(alpha)-methylhistamine on intestinal transit were examined in mice. The passage of a charcoal meal in the gastrointestinal tract was dose dependently inhibited by N(alpha)-methylhistamine (1-20 mg/kg i.p.), but not by a selective H-3 receptor agonist (R)alpha-methyl-histamine (1-50 mg/kg i.p.). The inhibitory effect of N(alpha)-methylhistamine (20 mg/kg) was attenuated by pretreatment with H-1 receptor antagonists (mepyramine 5 mg/kg i.p. or 5 mug i.c.v. and triprolidine 5 mg/kg i.p.), but not by cimetidine (10 mg/kg i.p.), zolantidine (5 mg/kg i.p.), a brain-penetrating H-2 receptor antagonist, or thioperamide (5 mg/kg i.p.), a selective H-3 receptor antagonist. The effect of N(alpha)-methylhistamine was also attenuated by combined treatment with phentolamine and propranolol (5 and 15 mg/kg s.c., respectively) and by pretreatment with 6-hydroxydopamine (20 mg/kg i.p., 2 days before). N(alpha)-Methylhistamine markedly decreased histamine turnover in the mouse brain. These findings suggest that intestinal transit is inhibited by N(alpha)-methylhistamine via stimulation of central H-1 but not H-3 receptors and that stimulation of the sympathetic system is involved in this effect.