Metoprine, an inhibitor of histamine N-methyltransferase but not catechol-O-methyltransferase, suppresses feeding in sated and in food deprived rats.
Metoprine is a histamine N-methyltransferase (HMT) inhibitor often used to elevate endogenous histamine (HA) levels when studying the role of brain HA. Since central histaminergic systems may be involved in the regulation of feeding, the effect of metoprine on food intake was studied in sated and in food deprived rats. The treatment caused a dose-dependent decrease in food intake in sated rats. It also suppressed deprivation-induced feeding. To clarify the specificity of the treatment, the effect of metoprine on another methylating enzyme, catechol-O-methyltransferase (COMT), was examined indirectly by examining the ratio of the non-methylated dopamine metabolite, dihydroxyphenylacetic acid (DOPAC) to that of its methylated product homovanillic acid (HVA). The dopamine metabolites did not change in a manner consistent with COMT inhibition, but instead a transient decrease in DOPAC levels was observed. However, the suppression of feeding is considered to be related to the metoprine-induced inhibition of brain HA catabolism and not with the changes in dopaminergic systems. Metoprine had no effect on brain concentration of serotonin (5-HT) or its metabolite 5-hydroxyindoleacetic acid (5-HIAA). The results provide further support for the role of brain HA in the control of feeding behavior.
Lecklin
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A
Department of Pharmacology and Toxicology, University of Kuopio, Finland.
Tuomisto
L
L
MacDonald
E
E
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002394:Catechol O-Methyltransferase / Q000187:drug effects* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects*; D005247:Feeding Behavior / Q000187:drug effects; D005493:Folic Acid Antagonists / Q000494:pharmacology*; D005508:Food Deprivation; D006637:Histamine N-Methyltransferase / Q000037:antagonists & inhibitors*; D006719:Homovanillic Acid / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D008745:Methylation; D011739:Pyrimethamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012527:Satiation / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism
D005493:Folic Acid Antagonists; D015102:3,4-Dihydroxyphenylacetic Acid; C006308:metoprine; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D002394:Catechol O-Methyltransferase; D006637:Histamine N-Methyltransferase; D006719:Homovanillic Acid; D011739:Pyrimethamine