Amodiaquine dihydrochloride dihydrate

Amodiaquine dihydrochloride dihydrate is a potent inhibitor of histamine N-methyltransferase (HNMT), with estimated K_i of 18.6 nM [1].

HNMT occurs ubiquitously in vertebrate species, and is widely expressed in mammalian tissues with particularly high expression levels in kidney, liver, colon, prostate, ovary, and spinal cord cells. HNMT is a cytosolic protein that is responsible for the intracellular inactivation of histamine [1].

Over the concentration range 10^-3 ~ 10^-8 M, amodiaquine was a significantly more potent inhibitor than other compounds including chlorhexidine, producing 80% inhibition on rat kidney HNMT at 10^-6 M whilst the next best inhibitor at this concentration, chlorhexidine, produced only 27% inhibition. [2].

In mice with Propionibacterium acnes-primed and lipopolysaccharide-induced hepatitis, the subcutaneous injection of amodiaquine at 2 and 5 mg/kg significantly increased the histamine levels in the liver. Pretreatment with amodiaquine also improved the survival rate of the hepatitis mice, which was partially associated with the decrease in serum levels of aspartate aminotransferase and alanine aminotransferase [3].

References:

[1]. Horton J R, Sawada K, Nishibori M, et al. Structural basis for inhibition of histamine N-methyltransferase by diverse drugs. Journal of Molecular Biology, 2005, 353(2): 334-344.

[2]. Harle D G, Baldo B A. Structural features of potent inhibitors of rat kidney histamine N-methyltransferase. Biochemical Pharmacology, 1988, 37(3): 385-388.

[3]. Yokoyama A, Mori S, Takahashi H K, et al. Effect of amodiaquine, a histamine N-methyltransferase inhibitor, on, Propionibacterium acnes and lipopolysaccharide-induced hepatitis in mice. European Journal of Pharmacology, 2007, 558(1-3): 179-184.