Actions of tacrine and galanthamine on histamine-N-methyltransferase.

Histamine-synthesizing neurons in the brain may play an important role in cognition, and a histaminergic deficit has been found in Alzheimer's disease (AD). The AD medication tacrine was previously shown to inhibit some forms of rodent histamine-N-methyltransferase (HNMT), but the effects of AD drugs have not been investigated on human HNMT activity. Presently, the effects of tacrine and galanthamine (another AD medication) were studied on the activity of several forms of human and rat HNMT. Tacrine (0.01-10 microM) inhibited both human and rat HNMT activity in a concentration-dependent manner, but was less potent on both human embryonic kidney and recombinant human brain HNMT than on rat kidney HNMT (IC50 values were 0.46 and 0.70 microM vs. 0.29 microM, respectively). Galanthamine (up to 10 microM) did not influence the activity of rat kidney or human HNMT. Tacrine, but not galanthamine, may achieve brain levels sufficient to influence histamine metabolism in some patients treated for AD.