ISSN:
1432-1912
Keywords:
Key words [3H]-Nα-methylhistamine binding
;
Rat brain cortex membranes
;
Mouse brain cortex slices
;
Histamine H3 receptors
;
Ciproxifan
;
Iodoproxyfan
;
Noradrenaline release
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract We determined the affinities of five newly synthesized histamine H3-receptor antagonists in an H3-receptor binding assay and their potencies in a functional H3-receptor model. Furthermore, we determined their potencies in a histamine H2- and H1-receptor model. The compounds differ from histamine in that the ethylamine side chain is replaced by an aryl-substituted propyloxy chain and they differ from one another by varying substituents of the aryl rest. Iodoproxyfan, a highly potent and selective antagonist at H3 receptors, is structurally related to these five compounds. The specific binding of [3H]-N α-methylhistamine to rat brain cortex membranes was monophasically displaced by each of the five compounds at pK i values ranging from 8.24 to 9.27. Inhibition by histamine of the electrically evoked tritium overflow from mouse brain cortex slices preincubated with [3H]noradrenaline was antagonized by all compounds and the concentration-response curve was shifted to the right with apparent pA 2 values ranging from 7.78 to 9.39. The five compounds under study possess negligible potencies at histamine H2 and H1 receptors studied in the guinea-pig right atrium and ileum, respectively (pD’2 or pK p values ≤5.2). The present paper shows that the five compounds under study possess high affinities and potencies at histamine H3 receptors, four out of the five compounds in this respect being equipotent with iodoproxyfan. Like iodoproxyfan, the five compounds show an at least 1000-fold selectivity for H3 as compared to H2 and H1 receptors.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/PL00005303
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