A5036532125- Neuroscience and Neuropharmacology Research
- Receptor Mechanisms and Signaling
- Chemical Synthesis and Analysis
- Ion channel regulation and function
- Phenothiazines and Benzothiazines Synthesis and Activities
- Pharmacological Receptor Mechanisms and Effects
- Molecular Sensors and Ion Detection
- Nicotinic Acetylcholine Receptors Study
- Memory and Neural Mechanisms
- Quinazolinone synthesis and applications
- Synthesis of Tetrazole Derivatives
- Chemical Synthesis and Reactions
- Biochemical Analysis and Sensing Techniques
- Molecular spectroscopy and chirality
- Organophosphorus compounds synthesis
- Pain Mechanisms and Treatments
- Neuropeptides and Animal Physiology
- Neuroinflammation and Neurodegeneration Mechanisms
- Regulation of Appetite and Obesity
- Multicomponent Synthesis of Heterocycles
- Biochemical and Molecular Research
- Photoreceptor and optogenetics research
- Fluorine in Organic Chemistry
- Synthesis and biological activity
- Treatment of Major Depression
Apollo Instruments (United States)
2021
Eli Lilly (United States)
2003-2019
Medical College of Wisconsin
2017-2018
Eli Lilly (United Kingdom)
2017
Roosevelt University
2017
Eli Lilly (Spain)
2002-2005
Albany Molecular Research (United States)
2004
IDELIX Software (Canada)
2000
University of Michigan
1986
University of Wisconsin–Madison
1981-1983
Glutamatergic hyperactivity is implicated migraine pathogenesis. Also, LY293558, an alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate (KA) receptor antagonist, effective in preclinical models of migraine. We therefore tested LY293558 acute conducted a randomized, triple-blind, parallel-group, double-dummy, multicentre trial 1.2 mg/kg intravenous (IV) 6 mg subcutaneous (SC) sumatriptan, or placebo the treatment The primary efficacy variable was headache response rate,...
A series of novel benzimidazoles (BI) derived from the indole 2 was synthesized and evaluated as selective neuropeptide Y (NPY) Y1 receptor antagonists with aim developing antiobesity drugs. In our SAR approach, (4-chlorophenoxy)methyl group at C-2 kept constant a BIs substituted various piperidinylalkyl groups N-1 to identify optimal spacing orientation piperidine ring nitrogen relative benzimidazole. The 3-(3-piperidinyl)propyl in 33 found maximize affinity for receptor. Because critical...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXT(3SR,4aRS,6RS,8aRS)-6-[2-(1H-Tetrazol-5-yl)ethyl]decahydroisoquinoline-3-carboxylic acid: a structurally novel, systemically active, competitive AMPA receptor antagonistPaul L. Ornstein, M. Brian Arnold, Nancy K. Augenstein, David Lodge, J. Leander, and Darryle D. SchoeppCite this: Med. Chem. 1993, 36, 14, 2046–2048Publication Date (Print):July 1, 1993Publication History Published online1 May 2002Published inissue 1 July...
The pharmacological tools available for the discrimination of kainate receptor subtypes are limited. We examined effects (3S,4aR,6R,8aR)-6-[2-(1(2)H-tetrazole-5-yl)ethyl]decahydr oisoquinoline-3-carboxylic acid (LY293558) and 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline (NBQX) on inward currents associated with activation non-N-methyl-D-asparate (NMDA) receptors in acutely isolated rat cerebellar Purkinje neurons, dorsal root ganglion human embryonic kidney 293 cells transfected...
Transmembrane AMPA receptor regulatory proteins (TARPs) are a family of scaffolding that regulate trafficking and function. TARP γ-8 is one member this highly expressed within the hippocampus relative to cerebellum. A selective γ-8-dependent antagonist (TDAA) an innovative approach modulate receptors in specific brain regions potentially increase therapeutic index known non-TARP-dependent antagonists. We describe here, for first time, discovery noncompetitive dependent on presence γ-8. Three...
In this paper we describe the synthesis of a series alpha-substituted analogues potent and selective group II metabotropic glutamate receptor (mGluR) agonist (1S,1'S,2'S)-carboxycyclopropylglycine (2, L-CCG 1). Incorporation substitutent on amino acid carbon converted 2 into an antagonist. All compounds were prepared tested as four isomers, i.e., two racemic diastereomers. On basis improvement in affinity realized for alpha-phenylethyl analogue 3, explored effects substitution aromatic ring...
[3H]LY341495 is a highly potent and selective antagonist for group II metabotropic glutamate (mGlu) receptors (mGlu2 mGlu3), which has been used to label these in cells expressing recombinant receptor subtypes. In this study, we characterized the kinetics, pharmacology, distribution of binding mGlu rat brain tissue. Equilibrium experiments forebrain demonstrated single site that was saturable, reversible, high affinity (Bmax, 3.9 +/- 0.65 pmol/mg protein, Kd, 0.84 0.11 nM). The relative...
The mechanisms underlying the neuroprotective effects of group II metabotropic glutamate receptor (mGluR) agonist LY379268 were investigated in a gerbil model global ischemia. (10 mg/kg i.p.) 30 or 60 min after 5-min bilateral carotid artery occlusion (BCAO) attenuated ischemia-induced hyperactivity and provided protection CA1 hippocampal cells. This effect was maintained (P <.001) when histological analysis performed 14 28 days BCAO. Furthermore, 24- 48-h pretreatment with LY379268, 10...