Discovery of novel lead in the group of N-substituted piperazine ether derivatives with potential histamine H3 receptor activity.

The search for novel lead from the group of various substituted N-piperazine ether derivatives was performed. Acyl- and pyridylpiperazine ethyl/propyl ethers were obtained via three different synthetic pathways. Affinity to histamine H3 receptor was established, as well as, for selected compounds, selectivity towards histamine H4R.

N-Alkenyl and cycloalkyl carbamates as dual acting histamine H3 and H4 receptor ligands.

Previous studies have shown that several imidazole derivatives possess affinity to histamine H(3) and H(4) receptors. Continuing our study on structural requirements responsible for affinity and selectivity for H(3)/H(4) receptor subtypes, two series of 3-(1H-imidazol-4-yl)propyl carbamates were prepared: a series of unsaturated alkyl derivatives (1-9) and a series possessing a cycloalkyl group different distances to the carbamate moiety (10-13). The compounds were tested for their affinities at the human histamine H(3) receptor, stably expressed in CHO-K1 cells.

Histamine elevates free intracellular calcium in mouse retinal dopaminergic cells via H1-receptors.

Purpose: Previously, retinopetal axons containing histamine and dopaminergic neurons expressing histamine H(1)-receptor had been localized in mouse retinas using anatomic techniques. The goal of these experiments was to demonstrate that these receptors are functional.

Methods: Dopaminergic cells were acutely isolated from retinas of transgenic mice expressing red fluorescent protein under control of the tyrosine hydroxylase promoter and loaded with the calcium indicator Fura-2.

Antihistaminic drugs modify casein-induced inflammation in the rat.

Introduction: All known antihistaminics may affect several inflammatory events, including chemotaxis, the survival of eosinophils, and the release of chemokines and cytokines from different sources, thus highlighting the potential for modulating chronic inflammation and immune responses. The aim of the study was to examine the effect of H(1)-H(4) antihistaminic drugs in an acute model of casein-induced inflammation in rat.

Materials And Methods: Inflammation was induced by injection of a 12% solution of casein into the peritoneal cavity of male Wistar rats.

Histamine H3 and H4 receptor affinity of branched 3-(1H-imidazol-4-yl)propyl N-alkylcarbamates.

A series of imidazole-containing (non-)chiral carbamates were tested at human histamine H(3) receptor (H(3)R). All compounds displayed K(i) values below 100 nM. A trend for a stereoselectivity at human H(3)R was observed for the chiral alpha-branched ligands.