Open Access9-Amino-1,2,3,4-Tetrahydroacridine Is a Potent Inhibitor of Histamine N-Methyltransferase.
Author(s) -
Masahiro Nishibori,
Ryozo Oishi,
Yoshinori Itoh,
Kiyomi Saeki
Publication year - 1991
Publication title -
japanese journal of pharmacology/japanese journal of pharmacology
Language(s) - English
Resource type - Journals
eISSN - 1347-3506
pISSN - 0021-5198
DOI - 10.1254/jjp.55.539
Subject(s) - histamine , histamine n methyltransferase , chemistry , physostigmine , in vivo , tacrine , pharmacology , methyltransferase , enzyme inhibitor , enzyme , in vitro , biochemistry , methylation , histamine h2 receptor , biology , antagonist , acetylcholine , acetylcholinesterase , receptor , microbiology and biotechnology , gene
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 Ki and Ki' values were 75 nM and 1.2 microM, respectively. The IC50 values for THA, 9-aminoacridine and physostigmine in the inhibition of HMT determined at fixed concentrations of histamine (20 microM) and S-adenosylmethionine (50 microM) were 0.2, 0.37 and 20 microM, respectively. Neostigmine exhibited only 15% inhibition even at a concentration of 100 microM. 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.