N alpha-methylhistamine inhibits intestinal transit in mice by central histamine H1 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 H3 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 H1 receptor antagonists (mepyramine 5 mg/kg i.p. or 5 micrograms 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 H2 receptor antagonist, or thioperamide (5 mg/kg i.p.), a selective H3 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 H1 but not H3 receptors and that stimulation of the sympathetic system is involved in this effect.
Oishi
R
R
Department of Pharmacology, Okayama University Medical School, Japan.
Adachi
N
N
Saeki
K
K
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004347:Drug Interactions; D005772:Gastrointestinal Transit / Q000187:drug effects*; D017442:Histamine Agonists / Q000494:pharmacology*; D006633:Histamine Antagonists; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D008297:Male; D008761:Methylhistamines / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D009638:Norepinephrine / Q000378:metabolism; D016627:Oxidopamine / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011969:Receptors, Histamine H1 / Q000187:drug effects*; D018100:Receptors, Histamine H3; D013050:Spectrometry, Fluorescence
D017442:Histamine Agonists; D006633:Histamine Antagonists; D006634:Histamine H1 Antagonists; D008761:Methylhistamines; D011969:Receptors, Histamine H1; D018100:Receptors, Histamine H3; C069357:alpha-methylhistamine; D016627:Oxidopamine; D011433:Propranolol; D009638:Norepinephrine; D010646:Phentolamine