Thomas M. Bare
Wilmington University
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Stroke | 1997
Kentaro Takano; Turgut Tatlisumak; James E. Formato; Richard A. D. Carano; Andreas Bergmann; Linda M. Pullan; Thomas M. Bare; Christopher H. Sotak; Marc Fisher
BACKGROUND AND PURPOSE The glycine site on the N-methyl-D-aspartate (NMDA) receptor complex offers a therapeutic target for acute focal ischemia, potentially devoid of most side effects associated with competitive and noncompetitive NMDA antagonists. METHODS A novel glycine receptor antagonist, ZD9379, was studied in 70 Sprague-Dawley rats using the suture occlusion model of permanent middle cerebral artery occlusion (MCAO). In the first experiment, 20 rats received an initial bolus of vehicle or 10 mg/kg ZD9379 (n = 10 in each group) 30 minutes after MCAO, followed by a continuous infusion of the same dose per hour for 4 hours. Diffusion-weighted MRI with echo-planar acquisition was used to generate maps of the apparent diffusion coefficient (ADC) of water. In a second experiment, 50 rats were assigned to five groups: vehicle and 10, 5, 2.5, and 1 mg/kg ZD9379 (n = 10 in each group) with the same dosing protocol but no imaging. In both experiments, infarct volume was determined by 2,3,5-triphenyltetrazolium chloride staining. RESULTS In the first experiment, before therapy was begun, there was no significant difference in ADC-derived ischemic lesion volume between the two groups. Over time, the 10-mg/kg ZD9379-treated rats had a significant delayed regional recovery of reduced ADC values in the peripheral parietal cortex (P = .0156). Postmortem corrected infarct volume at 24 hours after MCAO was significantly smaller in the group treated with 10 mg/kg ZD9379 than in the vehicle group (119.2 +/- 52.2 versus 211.2 +/- 50.0 mm3 [mean +/- SD]; P = .0008; a reduction of 43.6%). In the second experiment, postmortem corrected infarct volumes in rats receiving 10, 5, and 2.5 mg/kg ZD9379 were significantly smaller than in those receiving vehicle, a reduction of 42.6%, 51.4%, and 42.9%, respectively (P = .0001). CONCLUSIONS This study demonstrates that 2.5- to 10-mg/kg doses of ZD9379 initiated 30 minutes after MCAO significantly reduced infarct size. Diffusion mapping disclosed a delayed treatment effect of this glycine antagonist in focal ischemia, confirmed by the postmortem study.
Bioorganic & Medicinal Chemistry Letters | 1993
Thomas M. Bare; Clyde W. Draper; Charles D. McLaren; Linda M. Pullan; Jitendra Patel; Jitendra B. Patel
A series of novel spiroisoindolines was designed and synthesized as potential noncompetitive NMDA antagonists. Affinities of these compounds for the noncompetitive NMDA binding site were determined using [3H]TCP and found to possess IC50s ranging from 0.065 to 17μM. In vivo testing of 2′-methylspiro-[4,5,6,7-tetrahydrobenzothiophene-4,1′-(1,3-dihydroisoindole)] (43) showed it to antagonize NMDA-induced convulsions, to be neuroprotective in a gerbil model of ischemia, and not to generalize to MK-801 in a drug discrimination paradigm.
Journal of Medicinal Chemistry | 1989
Thomas M. Bare; Charles D. McLaren; James B. Campbell; Judy W. Firor; James F. Resch; Claudia P. Walters; Andre I. Salama; Brad A. Meiners; Jitendra Patel
Journal of Magnetic Resonance Imaging | 1997
Hui Qiu; Laurence W. Hedlund; Sally L. Gewalt; Helene Benveniste; Thomas M. Bare; G. Allan Johnson
Archive | 1983
Thomas M. Bare; Anthony F. Heald
Journal of Medicinal Chemistry | 2007
Thomas M. Bare; Dean G. Brown; Carey Horchler; Megan Murphy; Rebecca Urbanek; Vernon Alford; Christine Barlaam; Martin C. Dyroff; James B. Empfield; Janet Marie Forst; Keith J. Herzog; Richard Alan Keith; Alan S. Kirschner; Chi-Ming C. Lee; Joseph James Lewis; Frances M. Mclaren; Kathy L. Neilson; Gary Steelman; Shephali Trivedi; Edward P. Vacek; Wenhua Xiao
Archive | 1984
James B. Campbell; Thomas M. Bare
Archive | 1996
Thomas M. Bare; James Roy Empfield; Janet Marie Forst; Keith J. Herzog; Richard Bruce Sparks
Journal of Heterocyclic Chemistry | 1998
Thomas M. Bare
Archive | 1985
Thomas M. Bare