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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Stereoselective inhibition by chloroquine of histamine N-methyltransferase in the human liver and brain.

This study was designed to determine whether both enantiomers of chloroquine inhibit histamine N-methyltransferase. The mean estimates of IC50 for the d- and l-enantiomers of chloroquine were 4.9 and 17.8 microM (liver), respectively and 6.9 and 21.6 microM (brain), respectively. Ki estimates were significantly lower with d- than with l-chloroquine; hence, d-chloroquine interacts with the enzyme more effectively than l-chloroquine. If the adverse effects of chloroquine are due to the inhibition of histamine N-methyltransferase, therapy with the l-enantiomer might have lower toxicity. The residual activity of histamine N-methyltransferase should reflect both the degree of inhibition by chloroquine and the level of enzyme expression. The rate of histamine methylation was measured in 100 human liver samples and its range and fold of variation were 29% and threefold, respectively. Susceptibility to chloroquine should be greater in subjects with limited expression of histamine N-methyltransferase [1]

References

  1. Stereoselective inhibition by chloroquine of histamine N-methyltransferase in the human liver and brain. Donatelli, P., Marchi, G., Giuliani, L., Gustafsson, L.L., Pacifici, G.M. Eur. J. Clin. Pharmacol. (1994) [Pubmed]
 
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