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Radioreceptor Binding Profile of the Atypical Antipsychotic Olanzapine
TLDR
The receptor binding profile of olanzapine is consistent with the antidopaminergic, antiserotonergic, and antimuscarinic activity observed in animal models and predicts atypical antipsychotic activity in man. Expand
Robust Central Reduction of Amyloid-β in Humans with an Orally Available, Non-Peptidic β-Secretase Inhibitor
TLDR
The magnitude and duration of central Aβ reduction obtainable with BACE1 inhibition positions this protease as a tractable small-molecule target through which to test the amyloid hypothesis in man. Expand
Adipsin, a Biomarker of Gastrointestinal Toxicity Mediated by a Functional γ-Secretase Inhibitor*
TLDR
It is proposed that adipsin is a Hes-1-regulated gene that is de-repressed during FGSI-mediated disruption of Notch/Hes-1 signaling, and its presence in feces may serve as a noninvasive biomarker of gastrointestinal toxicity associated with perturbed Notch signaling. Expand
Xanomeline: a novel muscarinic receptor agonist with functional selectivity for M1 receptors.
TLDR
The present data are consistent with the interpretation that xanomeline is a novel muscarinic receptor agonist with functional selectivity for M1 mus carinic receptors both in vitro and in vivo. Expand
Preclinical pharmacological profile of the selective 5-HT1F receptor agonist lasmiditan
TLDR
Lasmiditan presents a unique pyridinoyl-piperidine scaffold not found in any other antimigraine class, whose chemical structure and pharmacological profile clearly distinguish it from the triptans. Expand
Pharmacological Characterization of the Competitive GLUK5 Receptor Antagonist Decahydroisoquinoline LY466195 in Vitro and in Vivo
TLDR
In vitro and in vivo pharmacology of the competitive GLUK5-selective kainate receptor antagonist LY466195 was examined, significantly reducing the number of Fos-positive cells in the rat nucleus caudalis after electrical stimulation of the trigeminal ganglion and showing no contractile activity in the rabbit saphenous vein in vitro. Expand
Characterization of LY344864 as a pharmacological tool to study 5-HT1F receptors: binding affinities, brain penetration and activity in the neurogenic dural inflammation model of migraine.
TLDR
Oral and intravenous LY344864 administration potently inhibited dural protein extravasation caused by electrical stimulation of the trigeminal ganglion in rats and demonstrated that LY 344864 is a selective 5-HT1F receptor agonist that can be used to explore both the in vitro and in vivo functions of this receptor. Expand
The Potent BACE1 Inhibitor LY2886721 Elicits Robust Central Aβ Pharmacodynamic Responses in Mice, Dogs, and Humans
TLDR
Nonclinical and early clinical development of LY2886721 is reported, a BACE1 active site inhibitor that reached phase 2 clinical trials in AD and has high selectivity against key off-target proteases, which efficiently translates in vitro activity into robust in vivo amyloid β lowering in nonclinical animal models. Expand
Xanomeline: A selective muscarinic agonist for the treatment of Alzheimer's disease
TLDR
Xanomeline was found to be safe and reasonably well tolerated in safety studies in humans, and halted cognitive decline in patients with Alzheimer's disease, in a placebo controlled double blind clinical trial of 6 months duration. Expand
Antagonism by olanzapine of dopamine D1, serotonin2, muscarinic, histamine H1 and α 1-adrenergic receptors in vitro
TLDR
Olanzapine was an antagonist at all receptors investigated and was a particularly potent antagonist at 5-HT2A, 5- HT2B, 5,HT2C, alpha 1-adrenergic and histamine H1 receptors. Expand
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