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153 results on '"Barrett, Terrance D."'

8. Effects of cyclooxygenase inhibition on canine coronary artery blood flow and thrombosis

Author

Hong, Ting-Ting, Huang, Jinbao, Barrett, Terrance D., and Lucchesi, Benedict R.

Subjects
COX-2 inhibitors -- Research, Cyclooxygenases -- Research, Coronary arteries -- Research, Blood flow -- Research, Blood clot -- Research, Thrombosis -- Research, Cardiovascular research, Biological sciences
Abstract

This study was designed to determine the effect of inhibitors of cyclooxygenase (COX)-1, COX-2, and the nonselective COX inhibitor naproxen on coronary vasoactivity and thrombogenicity under baseline and lipopolysaccharide (LPS)-induced inflammatory conditions. We hypothesize that endothelial COX-1 is the primary COX isoform in the canine normal coronary artery, which mediates arachidonic acid (AA)-induced vasodilatation. However, COX-2 can be induced and overexpressed by inflammatory mediators and becomes the major local COX isoform responsible for the production of antithrombotic prostaglandins during systemic inflammation. The interventions included the selective COX-1 inhibitor SC-560 (0.3 mg/kg iv), the selective COX-2 inhibitor nimesulide (5 mg/kg iv), or the nonselective COX inhibitor naproxen (3 mg/kg iv). The selective prostacyclin (IP) receptor antagonist RO-3244794 (RO) was used as an investigational tool to delineate the role of prostacyclin ([PGI.sub.2]) in modulating vascular reactivity. AA-induced vasodilatation of the left circumflex coronary artery was suppressed to a similar extent by each of the COX inhibitors and RO. The data suggest that AA-induced vasodilatation in the normal coronary artery is mediated by a single COX isoform, the constitutive endothelial COX-1, which is reported to be susceptible to COX-2 inhibitors. The effect of the COX inhibitors on thrombus formation was evaluated in a model of carotid artery thrombosis secondary to electrolytic-induced vessel wall injury. Pretreatment with LPS (0.5 mg/kg iv) induced a systemic inflammatory response and prolonged the time-to-occlusive thrombus formation, which was reduced in the LPS-treated animals by the administration of nimesulide. In contrast, neither SC-560 nor naproxen influenced the time to thrombosis in the animals pretreated with LPS. The data are of significance in view of reported adverse cardiovascular events observed in clinical trials involving the use of selective COX-2 inhibitors, thereby suggesting that the endothelial constitutive COX-1 and the inducible vascular COX-2 serve important functions in maintaining vascular homeostasis. inflammation; vascular reactivity

Published
2008

12. Effects of Canagliflozin on Heart Failure Outcomes Associated With Preserved and Reduced Ejection Fraction

Author

Figtree, Gemma A., Rådholm, Karin, Barrett, Terrance D., Perkovic, Vlado, Mahaffey, Kenneth W., de Zeeuw, Dick, Fulcher, Greg, Matthews, David R., Shaw, Wayne, and Neal, Bruce

Subjects
Medicinska och farmaceutiska grundvetenskaper, Basic Medicine, canagliflozin, heart failure, randomized trial, SGLT2 inhibitor, type 2 diabetes mellitus
Abstract

n/a Funding Agencies|Janssen Research & Development, LLC

Published
2019

13. Beyond Traditional Structure-Based Drug Design: The Role of Iron Complexation, Strain, and Water in the Binding of Inhibitors for Hypoxia-Inducible Factor Prolyl Hydroxylase 2

Author

Bembenek, Scott D., primary, Venkatesan, Hariharan, additional, Peltier, Hillary M., additional, Rosen, Mark D., additional, Barrett, Terrance D., additional, Kanelakis, Kimon C., additional, Palomino, Heather L., additional, Brondstetter, Theresa I., additional, Mirzadegan, Taraneh, additional, and Rabinowitz, Michael H., additional

Published
2019
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15. Tedisamil and lidocaine enhance each other's antiarrhythmic activity against ischaemia-induced arrhythmias in rats

Author

Sarraf, Guilda, Barrett, Terrance D, and Walker, Michael J A

Subjects
Cyclopropanes, Dose-Response Relationship, Drug, Myocardial Ischemia, Lidocaine, Arrhythmias, Cardiac, Blood Pressure, Drug Synergism, Bridged Bicyclo Compounds, Heterocyclic, Rats, Disease Models, Animal, Electrocardiography, Papers, Injections, Intravenous, Animals, Drug Therapy, Combination, Anti-Asthmatic Agents
Abstract

1. Combinations of the action potential-widening drug tedisamil (Class III antiarrhythmic activity), and the inactivated state sodium channel blocker lidocaine (Class Ib antiarrhythmic activity) were assessed for antiarrhythmic actions in a rat model of ischaemia-induced arrhythmias and for electrophysiological actions in normal rat myocardial tissue. 2. Both tedisamil and lidocaine dose-dependently suppressed ischaemia-induced arrhythmias. The ED(50) values were 3.0+/-1.3 and 4.9+/-0.6 micro mol kg(-1) min(-1), respectively. 3. Combinations of the two drugs acted synergistically such that the ED(50) for tedisamil was reduced to 0.8+/-0.2 micro mol kg(-1) min(-1) in the presence of 2 micro mol kg(-1) min(-1) lidocaine. Similarly, the ED(50) for lidocaine was reduced to 0.7+/-0.2 micro mol kg(-1) min(-1) in the presence of 2 micro mol kg(-1) min(-1) tedisamil (both P0.05). 4. In a separate series of experiments in which normal ventricular tissue was electrically stimulated, 2 micro mol kg(-1) min(-1) lidocaine produced a leftward shift in the dose-response curve for tedisamil's effect on effective refractory period (P0.05). This dose of lidocaine had no effect on its own. These data indicate that the synergistic actions of combinations of tedisamil and lidocaine were mediated, at least in part, by extension of effective refractory period in normal myocardial tissue. 5. In contrast to the strategy of developing drugs that are selective for a single electrophysiological mechanism, the results of the present study suggest that effective antiarrhythmic drugs might be developed by optimising the combination of two complimentary electrophysiological mechanisms (i.e., action potential-prolonging activity and inactivated state sodium channel blockade).

Published
2003

18. JNJ-26070109 [(R)4-Bromo-N-[1-(2,4-difluoro-phenyl)-ethyl]-2-(quinoxaline-5-sulfonylamino)-benzamide]: A Novel, Potent, and Selective Cholecystokinin 2 Receptor Antagonist with Good Oral Bioavailability

Author

Morton, Magda F., primary, Barrett, Terrance D., additional, Freedman, Jamie, additional, Li, Lina, additional, Rizzolio, Michele C., additional, Prendergast, Clodagh E., additional, Wu, Xiaodong, additional, Moreno, Veronica, additional, Pyati, Jayashree, additional, Figueroa, Katherine, additional, Cagnon, Laurence, additional, Lagaud, Guy, additional, Ver Donck, Luc, additional, Ghoos, Etienne, additional, Allison, Brett, additional, Rabinowitz, Michael H., additional, and Shankley, Nigel P., additional

Published
2011
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20. Pharmacological Characterization of 1-(5-Chloro-6-(trifluoromethoxy)-1H-benzoimidazol-2-yl)-1H-pyrazole-4-carboxylic Acid (JNJ-42041935), a Potent and Selective Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor

Author

Barrett, Terrance D., primary, Palomino, Heather L., additional, Brondstetter, Theresa I., additional, Kanelakis, Kimon C., additional, Wu, Xiaodong, additional, Haug, Peter V., additional, Yan, Wen, additional, Young, Andrew, additional, Hua, Hong, additional, Hart, Juliet C., additional, Tran, Da-Thao, additional, Venkatesan, Hariharan, additional, Rosen, Mark D., additional, Peltier, Hillary M., additional, Sepassi, Kia, additional, Rizzolio, Michele C., additional, Bembenek, Scott D., additional, Mirzadegan, Tara, additional, Rabinowitz, Michael H., additional, and Shankley, Nigel P., additional

Published
2011
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21. Benzimidazole-2-pyrazole HIF Prolyl 4-Hydroxylase Inhibitors as Oral Erythropoietin Secretagogues

Author

Rosen, Mark D., primary, Venkatesan, Hariharan, additional, Peltier, Hillary M., additional, Bembenek, Scott D., additional, Kanelakis, Kimon C., additional, Zhao, Lucy X., additional, Leonard, Barry E., additional, Hocutt, Frances M., additional, Wu, Xiaodong, additional, Palomino, Heather L., additional, Brondstetter, Theresa I., additional, Haugh, Peter V., additional, Cagnon, Laurence, additional, Yan, Wen, additional, Liotta, Lisa A., additional, Young, Andrew, additional, Mirzadegan, Tara, additional, Shankley, Nigel P., additional, Barrett, Terrance D., additional, and Rabinowitz, Michael H., additional

Published
2010
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22. Corrigendum to “Discovery of the first known small-molecule inhibitors of heme-regulated eukaryotic initiation factor 2α (HRI) kinase” [Bioorg. Med. Chem. Lett. 19 (2009) 6548]

Author

Rosen, Mark D., primary, Woods, Craig R., additional, Goldberg, Steven D., additional, Hack, Michael D., additional, Dawn Bounds, A., additional, Yang, Young, additional, Wagaman, Pamela C., additional, Phuong, Victor K., additional, Ameriks, Angela P., additional, Barrett, Terrance D., additional, Kanelakis, Kimon C., additional, Chuang, Jui Chang, additional, Shankley, Nigel P., additional, and Rabinowitz, Michael H., additional

Published
2010
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27. 3-[5-(3,4-Dichloro-phenyl)-1-(4-methoxy-phenyl)-1H-pyrazol-3-yl]-2-m-tolyl-propionate (JNJ-17156516), a Novel, Potent, and Selective Cholecystokinin 1 Receptor Antagonist: In Vitro and in Vivo Pharmacological Comparison with Dexloxiglumide

Author

Morton, Magda F., primary, Barrett, Terrance D., additional, Yan, Wen, additional, Freedman, Jamie M., additional, Lagaud, Guy, additional, Prendergast, Clodagh E., additional, Moreno, Veronica, additional, Pyati, Jayashree, additional, Figueroa, Katherine, additional, Li, Lina, additional, Wu, Xiaodong, additional, Rizzolio, Michele, additional, Breitenbucher, James G., additional, McClure, Kelly, additional, and Shankley, Nigel P., additional

Published
2007
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28. Synthesis and Biological Studies of Novel 2-Aminoalkylethers as Potential Antiarrhythmic Agents for the Conversion of Atrial Fibrillation

Author

Plouvier, Bertrand, primary, Beatch, Gregory N., additional, Jung, Grace L., additional, Zolotoy, Alexander, additional, Sheng, Tao, additional, Clohs, Lilian, additional, Barrett, Terrance D., additional, Fedida, David, additional, Wang, Wei Q., additional, Zhu, Jeff J., additional, Liu, Yuzhong, additional, Abraham, Shlomo, additional, Lynn, Leah, additional, Dong, Ying, additional, Wall, Richard A., additional, and Walker, Michael J. A., additional

Published
2007
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45. Better antiarrhythmics? Development of antiarrhythmic drugs selective for ischaemia-dependent arrhythmias

Author

Bain, Allen I., primary, Barrett, Terrance D., additional, Beatch, Gregory N., additional, Fedida, David, additional, Hayes, Eric S., additional, Plouvier, Bertrand, additional, Pugsley, Michael K., additional, Walker, Michael J.A., additional, Walker, Mariah L., additional, Wall, Richard A., additional, Yong, Sandro L., additional, and Zolotoy, Alexander, additional

Published
1997
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48. Effects of cyclooxygenase inhibition on canine coronary artery blood flow and thrombosis.

Author

Ting-Ting Hong, Jinbao Huang, Barrett, Terrance D., and Lucchesi, Benedict R.

Subjects
CYCLOOXYGENASES, CORONARY arteries, ANIMAL models in research, BLOOD flow, THROMBOSIS, INFLAMMATION
Abstract

This study was designed to determine the effect of inhibitors of cyclooxygenase (COX)-1, COX-2, and the nonselective COX inhibitor naproxen on coronary vasoactivity and thrombogenicity under baseline and lipopolysaccharide (LPS)-induced inflammatory conditions. We hypothesize that endothelial COX-1 is the primary COX isoform in the canine normal coronary artery, which mediates arachidonic acid (AA)-induced vasodilatation. However, COX-2 can be induced and overexpressed by inflammatory mediators and becomes the major local COX isoform responsible for the production of antithrombotic prostaglandins during systemic inflammation. The interventions included the selective COX-1 inhibitor SC-560 (0.3 mg/kg iv), the selective COX-2 inhibitor nimesulide (5 mg/kg iv), or the nonselective COX inhibitor naproxen (3 mg/kg iv). The selective prostacyclin (IP) receptor antagonist RO-3244794 (RO) was used as an investigational tool to delineate the role of prostacyclin (PGI2) in modulating vascular reactivity. AA-induced vasodilatation of the left circumflex coronary artery was suppressed to a similar extent by each of the COX inhibitors and RO. The data suggest that AA-induced vasodilatation in the normal coronary artery is mediated by a single COX isoform, the constitutive endothelial COX-1, which is reported to be susceptible to COX-2 inhibitors. The effect of the COX inhibitors on thrombus formation was evaluated in a model of carotid artery thrombosis secondary to electrolytic-induced vessel wall injury. Pretreatment with LPS (0.5 mg/kg iv) induced a systemic inflammatory response and prolonged the time-to-occlusive thrombus formation, which was reduced in the LPS-treated animals by the administration of nimesutide. In contrast, neither SC-560 nor naproxen influenced the time to thrombosis in the animals pretreated with LPS. The data are of significance in view of reported adverse cardiovascular events observed in clinical trials involving the use of selective COX-2 inhibitors, thereby suggesting that the endothelial constitutive COX-1 and the inducible vascular COX-2 serve important functions in maintaining vascular homeostasis. [ABSTRACT FROM AUTHOR]

Published
2008
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49. Glibenclamide Does Not Prevent Action Potential Shortening Induced by Ischemia in Anesthetized Rabbits But Reduces Ischemia-induced Arrhythmias

Author

Barrett, Terrance D. and Walker, Michael J.A.

Abstract

The possible ischemia-selective Class III anti-arrhythmic action (selective action potential widening in ischemia) of the IKATPblocker glibenclamide was assessed in anesthetized rabbits during ischemia induced by complete occlusion of a coronary artery. Coronary artery occlusion caused an intitial prolongation in monophasic action potential (MAP) duration at 90% repolarization from 145±2.8 ms (mean±s.e.m.,n=14) to 162±4.5 ms (P<0.05) 1 min after ischemia. This was followed by a rapid and sustained shortening to 104±4.9 ms 5 min after the onset of ischemia (P<0.05 from both values). Glibenclamide (3, 6, 12 or 24 mg/kg, i.v.) caused a statistically significant, dose-related reduction in the rate of MAP shortening induced by ischemia, whereas 0.3 mg/kg was without effect. The effective dose for a 50% maximal effect (ED50) was 13±0.8 mg/kg (n=28). Despite this, there was no effect on the final magnitude of MAP shortening. Five min after induction of ischemia, there were no longer any detectable effects of glibenclamide on MAP duration. Glibenclamide significantly reduced the incidence of ventricular fibrillation, although the effect was not dose related. No differences were found in the latency to ventricular fibrillation between groups. Ventricular fibrillation occurred 10.6±1.1 min (n=19) after the start of ischemia. In a similar experiment, 0.3 mg/kg glibenclamide i.v. did not affect the rate of MAP shortening, the final magnitude of MAP shortening or the occurrence of arrhythmias caused by ischemia. Since the action potential widening effects of glibenclamide in ischemic tissue were not observed at the time when arrhythmias occurred, it is unlikely that an ischemia-selective Class III anti-arrhythmic action contributes to the limited antiarrhythmic actions of glibenclamide.

Published
1998
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50. SAR studies of 1,5-diarylpyrazole-based CCK1 receptor antagonists

Author

Gomez, Laurent, Hack, Michael D., McClure, Kelly, Sehon, Clark, Huang, Liming, Morton, Magda, Li, Lina, Barrett, Terrance D., Shankley, Nigel, and Breitenbucher, J. Guy

Subjects
*PHARMACEUTICAL chemistry, *CHEMISTRY, *HIGH throughput screening (Drug development), *INCOMPATIBLES (Pharmacy)
Abstract

Abstract: A high throughput screening campaign revealed compound 1 as a potent antagonist of the human CCK1 receptor. Here, we report the syntheses and SAR studies of 1,5-diarylpyrazole analogs with various structural modifications of the alkane side chain of the molecule. The difference in affinity between the two enantiomers for the CCK1 receptor and the flexible nature of the linker led to the design of constrained analogs with increased potency. [Copyright &y& Elsevier]

Published
2007
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