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Description: A-304121, a piperazine amide, is a potent H3R antagonist. A-304121 potently antagonize native H3Rs by blocking histamine inhibition of potassium-evoked 3Hhistamine release from rat brain cortical synaptosomes (pKb values = 8.6 and 9.3) and (R)-alpha-MeHA reversal of electric field-stimulated guinea pig ileum contractions (pA2 values = 7.1 and 8.3). A-304121 is also more efficacious inverse agonists in reversing basal guanosine 5'-O-(3-35Sthio)triphosphate (35SGTP gamma S) binding at the human H3R (pEC50 values = 5.7 and 7.0) than are the imidazole antagonists. These novel and selective piperazine amides represent useful leads for the development of H3R antagonist therapeutic agents.
References: J Pharmacol Exp Ther. 2003 Jun; 305(3):887-96.
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