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.