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

Actions of betahistine at histamine receptors in the brain.

The actions of betahistine (N alpha-methyl-2-pyridylethylamine) on brain histamine receptors were investigated in a series of biological models. [3H]Mepyramine binding to H1-receptors in membranes from guinea-pig cerebellum was inhibited by betahistine with a Ki value of 31 microM. The binding of [3H]mepyramine in brain of the living mouse was inhibited by betahistine in high dosages (150-300 mg/kg). In slices from mouse cerebral cortex, betahistine induced [3H]glycogen hydrolysis in a concentration-dependent manner with an EC50 value of 9.0 microM with a maximal effect 57% that of histamine. Mepyramine and triprolidine, two H1-receptor antagonists, inhibited the betahistine-induced glycogenolysis with Ki values of 28 nM and 7 nM respectively. In slices from guinea-pig hippocampus, betahistine stimulated the accumulation of cyclic AMP in the presence of 5 microM impromidine, a H2-receptor agonist. The maximal effect represented 22% of that elicited by histamine at the H1-receptor and the EC50 value was 32.4 microM. Mepyramine at 0.1 microM partially blocked the response to betahistine. Together these various observations indicate that betahistine is a partial agonist at cerebral H1-receptors. Finally, betahistine was not an agonist at histamine H3-autoreceptors but was a rather potent antagonist of the inhibitory effect of exogenous histamine on [3H]histamine release elicited by K+ depolarisation in slices from rat cerebral cortex (Ki = 6.9 microM).[1]


  1. Actions of betahistine at histamine receptors in the brain. Arrang, J.M., Garbarg, M., Quach, T.T., Dam Trung TuongM, n.u.l.l., Yeramian, E., Schwartz, J.C. Eur. J. Pharmacol. (1985) [Pubmed]
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