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Histamine N‐methyl transferase: inhibition by drugs.
Author(s) -
Pacifici GM,
Donatelli P.,
Giuliani L.
Publication year - 1992
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.1992.tb05637.x
Subject(s) - histamine n methyltransferase , histamine , kidney , methyltransferase , medicine , chemistry , endocrinology , pharmacology , biology , methylation , biochemistry , receptor , histamine h2 receptor , gene , antagonist
1. Histamine N‐methyl transferase activity was measured in samples of human liver, brain, kidney, lung and intestinal mucosa. The mean (+/‐ s.d.) rate (nmol min‐1 mg‐1 protein) of histamine N‐methylation was 1.78 +/‐ 0.59 (liver, n = 60), 1.15 +/‐ 0.38 (renal cortex, n = 8), 0.79 +/‐ 0.14 (renal medulla, n = 8), 0.35 +/‐ 0.08 (lung, n = 20), 0.47 +/‐ 0.18 (human intestine, n = 30) and 0.29 +/‐ 0.14 (brain, n = 13). 2. Inhibition of histamine N‐methyl transferase by 15 drugs was investigated in human liver. The IC50 for the various drugs ranged over three orders of magnitude; chloroquine was the most potent inhibitor. 3. The average IC50 values for chloroquine were 12.6, 22.0, 19.0, 21.6 microM in liver, renal cortex, brain and colon, respectively. These values are lower than the Michaelis‐Menten constant for histamine N‐ methyltransferase in liver (43.8 microM) and kidney (45.5 microM). Chloroquine carried a mixed non‐competitive inhibition of hepatic histamine N‐methyl transferase. Some side‐effects of chloroquine may be explained by inhibition of histamine N‐methyl transferase.