Pharmacological profile of new thioperamide derivatives at histamine peripheral H1-, H2-, H3-receptors in guinea-pig

The recent availability of potent and selective ligands, namely R-()-methylhistamine and thioperamide, led to conclusive progresses as regards histamine H₃-receptor knowledge. The aim of this work is to investigate byin vitro tests the pharmacological properties of new amino and methyl derivatives of the H₃-antagonist thioperamide. Such original compounds, developed by the modulation of the thioperamide imidazolyl moiety, were assayed at guinea-pig ileal contractile H₁-, atrial chronotropic H₂- and enteric neuronal H₃-receptors.None of the drugs exhibited interaction with H₁ or H₂ sites. On electrically stimulated ileum, two of the thioperamide methyl derivatives competitively antagonized the inhibitory effect of the H₃-agonist R-()-methylhistamine. On the basis of the Schild analysis, the more active isomer (compound IV) displayed an affinity at H₃-receptors only five times lower than thioperamide. These results could contribute to elucidate further the structural features required to develop potent and selective H₃-antagonists. On the other hand, to prove the hypothesized apparent heterogeneity between peripheral and central H₃-sites, as emerged by pharmacological and binding studies, autoradiographic investigations are in progress.     

The influence of histamine H1-, H2- and H3-receptor antagonists on histamine stimulated NGF release from cultured astrocytes

Inflammation Research -