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.
Cumming
P
P
Montreal Neurological Institute, Quebec, Canada.
Vincent
S R
SR
D000818:Animals; D001921:Brain / Q000201:enzymology*; D002243:Carbolines / Q000494:pharmacology*; D006213:Hallucinogens / Q000494:pharmacology; D006246:Harmaline / Q000494:pharmacology; D006632:Histamine / Q000378:metabolism; D006637:Histamine N-Methyltransferase / Q000037:antagonists & inhibitors*; D016015:Logistic Models; D011802:Quinidine / Q000494:pharmacology; D051381:Rats; D012436:S-Adenosylmethionine / Q000378:metabolism; D013619:Tacrine / Q000494:pharmacology*
D002243:Carbolines; D006213:Hallucinogens; D013619:Tacrine; D012436:S-Adenosylmethionine; D006632:Histamine; D006246:Harmaline; D006637:Histamine N-Methyltransferase; D011802:Quinidine