The blockade of H1 receptors attenuates the suppression of feeding and diuresis induced by inhibition of histamine catabolism.
Metoprine elevates brain histamine content by blocking the conversion of histamine to methylhistamine. It suppresses food intake, increases water intake. and induces diuresis in rats. In the present experiment, to study which receptors were involved in these metoprine-induced changes, H1, H2, and H3 receptor blockers were administered to metoprine (10 mg/kg IP)-treated rats. The food and water consumption and urine excretion were measured at 10 and 24 h after the drug administration. It was found that systemic administration of the H3 receptor antagonist, thioperamide (5 mg/kg IP), supplemented the feeding suppressive effect of metoprine. In addition to this, the H1 receptor antagonist mepyramine (20 mg/kg IP) antagonized the suppression of feeding in metoprine-treated rats, whereas the H2 receptor antagonist, ranitidine (100 mg/kg IP), had no effect. Mepyramine also decreased the diuretic response to metoprine, whereas ranitidine or thioperamide were virtually without effect. The present results show that elevation of brain histamine content by inhibiting the catabolism of histamine suppresses food intake, and this effect of metoprine can be abolished by pretreatment with antihistamines. Although the blockade of H1 receptors also attenuates the diuretic response to metoprine, further studies are needed to understand the mechanisms that mediate the effects of metoprine on water balance.
Lecklin
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A
Department of Pharmacology and Toxicology, University of Kuopio, Finland.
Tuomisto
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L
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D004231:Diuresis / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005247:Feeding Behavior / Q000187:drug effects*; D006632:Histamine / Q000378:metabolism*; D006633:Histamine Antagonists / Q000494:pharmacology; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D008297:Male; D010880:Piperidines / Q000494:pharmacology; D011738:Pyrilamine / Q000494:pharmacology; D011739:Pyrimethamine / Q000031:analogs & derivatives / Q000494:pharmacology; D011899:Ranitidine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014882:Water-Electrolyte Balance / Q000187:drug effects
D004791:Enzyme Inhibitors; D006633:Histamine Antagonists; D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D010880:Piperidines; C006308:metoprine; D006632:Histamine; D011899:Ranitidine; D011738:Pyrilamine; C052075:thioperamide; D011739:Pyrimethamine