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

Actions of the brain-penetrating H2-antagonist zolantidine on histamine dynamics and metabolism in rat brain.

The effects of zolantidine, the first brain-penetrating H2-receptor antagonist, on the brain levels of histamine (HA) and the HA metabolite tele-methylhistamine (t-MH), the activity of histamine methyltransferase ( HMT) and the brain HA turnover rates were investigated in rats. Zolantidine dimaleate (0.1 to 100 mg/kg, s.c.) had no effect on whole brain levels of HA or t-MH and no effect on brain HMT activity, when measured 30 min after administration. Furthermore, brain t-MH levels in pargyline-treated animals were unaffected by zolantidine (0.1 to 25 mg/kg), indicating the absence of an effect on brain HA turnover. In vitro, zolantidine was a potent competitive inhibitor of both brain and kidney HMT, with Ki values of 2.3 and 2.7 microM respectively. These results show that, despite the ability of zolantidine to inhibit HMT in vitro, large doses of this drug did not alter brain HA methylation or turnover in vivo, and they imply that blockade of post-synaptic H2-receptors does not change brain HA dynamics.[1]

References

  1. Actions of the brain-penetrating H2-antagonist zolantidine on histamine dynamics and metabolism in rat brain. Hough, L.B., Jackowski, S., Eberle, N., Gogas, K.R., Camarota, N.A., Cue, D. Biochem. Pharmacol. (1988) [Pubmed]
 
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