Inhibition of histamine versus acetylcholine metabolism as a mechanism of tacrine activity.
Following tacrine administration i.p. to mice, the histamine N-methyltransferase activity of brain homogenates was more potently inhibited than the acetylcholinesterase activity (ID50 of 5.3 mg/kg vs. 13.6 mg/kg). The formation of the metabolite, tele-methylhistamine, in brain of mice treated with an histamine H3 receptor antagonist was abolished by tacrine with an ID50 as low as 1.2 +/- 0.4 mg/kg. The participation of histamine in the actions of tacrine and the relevance of histamine H3 receptor antagonists in Alzheimer's disease are suggested.
Morisset
S
S
Unité de Neurobiologie et Pharmacologie (U. 109) de l'INSERM, Centre Paul Broca, Paris, France.
Traiffort
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E
Schwartz
J C
JC
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000201:enzymology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006633:Histamine Antagonists / Q000494:pharmacology; D006637:Histamine N-Methyltransferase / Q000037:antagonists & inhibitors*; D008297:Male; D008761:Methylhistamines / Q000378:metabolism; D051379:Mice; D018697:Nootropic Agents / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology; D013619:Tacrine / Q000494:pharmacology*
D002800:Cholinesterase Inhibitors; D006633:Histamine Antagonists; D008761:Methylhistamines; D018697:Nootropic Agents; D010880:Piperidines; D013619:Tacrine; D006637:Histamine N-Methyltransferase; C052075:thioperamide; C020404:tele-methylhistamine