Inhibition of histamine-N-methyltransferase (HNMT) by fragments of 9-amino-1,2,3,4-tetrahydroacridine (tacrine) and by beta-carbolines.

Histamine-N-methyltransferase (HNMT), the major enzyme for the metabolism of histamine in rat brain, is potently inhibited by 9-amino-1,2,3,4-tetrahydroacridine (tacrine). Structural fragments of tacrine were less potent inhibitors of rat brain HNMT than was tacrine itself. Harmaline and a number of other beta-carbolines inhibited HNMT with IC50 values in the range of 1-10 microM. HNMT inhibition by harmaline was competitive with respect to both substrates, S-adenosylmethionine and histamine (Ki = 1.4 microM). These findings are discussed in the context of mechanisms for HNMT inhibition.