Publications by authors named "M Capet"

Aims: To characterise the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of single ascending doses of oxathridine, a first-in-class histamine-3 receptor partialagonist, in healthy male volunteers.

Methods: A randomised, double-blind, placebo-controlled study including the NeuroCart, consisting of a battery of drug sensitive neurophysiological tests, was performed. Oxathridine was administered orally as an aqueous solution.

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Background And Purpose: BF2.649 (pitolisant, Wakix®) is a novel histamine H receptor inverse agonist/antagonist recently approved for the treatment of narcolepsy disorder. The objective of the study was to investigate in vivo occupancy of H receptors by BF2.

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Since the discovery and early characterization of the histamine H receptor (HR) in the 1980's, predominantly imidazole-based agonists were presented to the scientific community such as N-methylhistamine (N-MeHA) or (R)-α-methylhistamine ((R)α-MeHA). Whereas therapeutic applications have been prompted for HR agonists such as treatment of pain, asthma and obesity, several drawbacks associated with imidazole-containing ligands makes the search for new agonists for this receptor demanding. Accordingly, high interest arose after publication of several pyrrolidindione-based, highly affine HR agonists within this journal that avoid the imidazole moiety and thus, presenting a novel type of potential pharmacophores (Ghoshal, Anirban et al.

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Synthesis and biological evaluation of a new class of histamine H receptor ligands, distinct from the previously reported chemotypes, are described. A virtual screening of our corporate compound collection identified a hit with an undesired dual H3R/H4R activity. Chemical exploration led to the discovery of a more potent and selective 2-benzothiazolylphenylmethyl ether lead compound.

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The involvement of histamine H4 receptor (H4R) in immune cells chemotaxis and mediator release makes it an attractive target for the treatment of inflammation disorders. A decade of medicinal chemistry efforts has led to several promising ligands, although the chemical structures described so far possesses a singular limited diversity. We report here the discovery of novel structures, belonging to completely different scaffolds.

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