9-Amino-1,2,3,4-tetrahydroacridine is a potent inhibitor of histamine N-methyltransferase

Masahiro Nishibori, R. Oishi, Y. Itoh, K. Saeki

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Abstract

The effect of 9-amino-1,2,3,4-tetrahydroacridine (THA) on histamine N-methyltransferase (HMT), an enzyme catalyzing the methylation of histamine to form tele-methylhistamine in the brain, was studied in vitro using a partially purified enzyme preparation from bovine brain and in vivo in the mouse brain. THA inhibited the HMT activity in competitive and non-competitive mixed type manners with respect to histamine. The K(i) and K(i), values were 75 nM and 1.2 μM, respectively. The IC50 values for THA, 9-aminoacridine and physostigmine in the inhibition of HMT determined at fixed concentrations of histamine (20 μM) and S-adenosylmethionine (50 μM) were 0.2, 0.37 and 20 μM, respectively. Neostigmine exhibited only 15% inhibition even at a concentration of 100 μM. THA (2-10 mg/kg, s.c.) dose-dependently inhibited HMT in the mouse brain. The inhibition of HMT by THA (10 mg/kg) was marked at 30 and 60 min after treatment, but disappeared by 120 min after. THA (10 mg/kg) significantly increased the histamine level and decreased the tele-methylhistamine level in the mouse brain. These results indicate that THA is a potent inhibitor of HMT.

Original languageEnglish
Pages (from-to)539-546
Number of pages8
JournalJapanese Journal of Pharmacology
Volume55
Issue number4
Publication statusPublished - 1991

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ASJC Scopus subject areas

  • Pharmacology

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