- Axitinib is an active treatment for all histologic subtypes of advanced thyroid cancer: results from a phase II study
Ezra E W Cohen
Section of Hematology Oncology, Department of Medicine, University of Chicago Division of Biological Sciences, 5801 S Ellis, Chicago, IL 60637, USA
J Clin Oncol 26:4708-13. 2008
..This multi-institutional study assessed the activity and safety of axitinib, an oral, potent, and selective inhibitor of vascular endothelial growth factor receptors (VEGFR) 1, 2, and 3 in patients with advanced thyroid cancer...
- Phase I trial of the oral antiangiogenesis agent AG-013736 in patients with advanced solid tumors: pharmacokinetic and clinical results
Hope S Rugo
University of California, San Francisco Comprehensive Cancer Center, USA
J Clin Oncol 23:5474-83. 2005
..The unique phase I study design allowed early identification of important absorption and metabolic issues critical to phase II testing of this agent...
- Phase II study of axitinib in sorafenib-refractory metastatic renal cell carcinoma
Brian I Rini
Department of Solid Tumor Oncology and Urology, Cleveland Clinic Taussig Cancer Institute, 9500 Euclid Ave, Desk R35, Cleveland, OH 44195, USA
J Clin Oncol 27:4462-8. 2009
- New anticancer strategies targeting HIF-1
Department of Pharmacology, College of Medicine, Seoul National University, 28 Yongon-dong, Chongno-gu, 110-799, Republic of Korea
Biochem Pharmacol 68:1061-9. 2004
..Moreover, it halted tumor growth in immunodeficient mice without serious toxicity during the treatment period. Thus, we propose that YC-1 is a good lead compound for the development of new anti-HIF-1, anticancer agents...
- Efficacy of gemcitabine plus axitinib compared with gemcitabine alone in patients with advanced pancreatic cancer: an open-label randomised phase II study
Jean Philippe Spano
Hopital de la Pitie Salpetriere, Paris, France
Lancet 371:2101-8. 2008
..The aim of this study was to assess the safety and efficacy of gemcitabine plus axitinib versus gemcitabine alone...
- The identification of 2-(1H-indazol-4-yl)-6-(4-methanesulfonyl-piperazin-1-ylmethyl)-4-morpholin-4-yl-thieno[3,2-d]pyrimidine (GDC-0941) as a potent, selective, orally bioavailable inhibitor of class I PI3 kinase for the treatment of cancer
Adrian J Folkes
Piramed Pharma, 957 Buckingham Avenue, Slough, Berks SL1 4NL, United Kingdom
J Med Chem 51:5522-32. 2008
..This work resulted in the discovery of 17, GDC-0941, which is a potent, selective, orally bioavailable inhibitor of PI3K and is currently being evaluated in human clinical trials for the treatment of cancer...
- YC-1 inhibited human platelet aggregation through NO-independent activation of soluble guanylate cyclase
C C Wu
Pharmacological Institute, College of Medicine, National Taiwan University, Taipei
Br J Pharmacol 116:1973-8. 1995
..7. These results would suggest that YC-1 activates sGC of human platelets by a NO-dependent mechanism, and exerts its antiplatelet effects through the sGC/cyclic GMP pathway...
- Preclinical activity of ABT-869, a multitargeted receptor tyrosine kinase inhibitor
Daniel H Albert
Cancer Research, Global Pharmaceutical Research and Development, Abbott Laboratories, R47J, Building AP9 2, 100 Abbott Park Road, Abbott Park, IL 60064 3500, USA
Mol Cancer Ther 5:995-1006. 2006
..08 microg/mL, >or=7 hours) than with plasma area under the curve or Cmax. These results support clinical assessment of ABT-869 as a therapeutic agent for cancer...
- Enhanced activation of STAT pathways and overexpression of survivin confer resistance to FLT3 inhibitors and could be therapeutic targets in AML
Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
Blood 113:4052-62. 2009
- Synergistic antileukemic effects between ABT-869 and chemotherapy involve downregulation of cell cycle-regulated genes and c-Mos-mediated MAPK pathway
Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
Leukemia 22:138-46. 2008
..Thus, a clinical trial using sequence-dependent combination therapy with ABT-869 in AML is warranted...
- Phase II study of lonidamine and diazepam in the treatment of recurrent glioblastoma multiforme
Department of Oncology, Hopital Europeen Georges Pompidou, Paris, France
J Neurooncol 63:81-6. 2003
..LND plus diazepam may be interesting in the adjuvant setting or associated to chemotherapy to act on different targets and increase the therapeutic index...
- ABT-869, a multitargeted receptor tyrosine kinase inhibitor: inhibition of FLT3 phosphorylation and signaling in acute myeloid leukemia
Deepa B Shankar
Division of Hematology Oncology, Department of Pediatrics, Gwynne Hazen Cherry Memorial Laboratories, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA
Blood 109:3400-8. 2007
..In tumors, ABT-869 inhibited FLT3 phosphorylation, induced apoptosis (transferase-mediated dUTP nick-end labeling [TUNEL]) and decreased proliferation (Ki67). ABT-869 is under clinical development for AML...
- Mitochondrial targeting drug lonidamine triggered apoptosis in doxorubicin-resistant HepG2 cells
Y C Li
Department of Biochemistry, The Chinese University of Hong Kong, Shatin, People's Republic of China
Life Sci 71:2729-40. 2002
..Taken together, our results suggest a potential use of LND as an anti-cancer drug to bypass drug resistance and to trigger tumour destruction through apoptosis in HepG2 and R-HepG2 cells...
- Effect of rifampin on the pharmacokinetics of Axitinib (AG-013736) in Japanese and Caucasian healthy volunteers
Y K Pithavala
Pfizer Oncology, Pfizer Global Research and Development, La Jolla Laboratories, 101646 Science Center Drive, San Diego, CA 92121, USA
Cancer Chemother Pharmacol 65:563-70. 2010
..Equal numbers of Japanese and Caucasian subjects were enrolled to assess the potential differences in axitinib pharmacokinetics between the two ethnicities...
- Nonclinical antiangiogenesis and antitumor activities of axitinib (AG-013736), an oral, potent, and selective inhibitor of vascular endothelial growth factor receptor tyrosine kinases 1, 2, 3
Dana D Hu-Lowe
Department of Cancer Biology, PGRD La Jolla, Pfizer, Inc, San Diego, California 92121, USA
Clin Cancer Res 14:7272-83. 2008
..We provide a comprehensive description of its in vitro characteristics and activities, in vivo antiangiogenesis, and antitumor efficacy and translational pharmacology data...
- Protective effects of YC-1 against glutamate induced PC12 cell apoptosis
College of Medicine, Nankai University, Tianjin, China
Cell Mol Neurobiol 31:303-11. 2011
..These results revealed that YC-1 might attenuate glutamate-induced PC12 cell apoptosis via a sGC-cGMP involved pathway...
- Inhibitory mechanisms of YC-1 and PMC in the induction of iNOS expression by lipoteichoic acid in RAW 264.7 macrophages
Graduate Institute of Pharmacology, Taipei Medical University, 250 Wu-Shing Street, Taipei 110, Taiwan, ROC
Biochem Pharmacol 67:1411-9. 2004
..YC-1 may be mediated by increasing cyclic GMP, followed by, at least partly, inhibition of JNK/SAPK and NF-kappaB activations, thereby leading to inhibition of iNOS expression...
- YC-1 inhibits HIF-1 expression in prostate cancer cells: contribution of Akt/NF-kappaB signaling to HIF-1alpha accumulation during hypoxia
H L Sun
Pharmacological Institute, College of Medicine, National Taiwan University, Taipei, Taiwan
Oncogene 26:3941-51. 2007
..Overall, we identify a potential molecular mechanism whereby YC-1 serves to reduce HIF-1 expression...
- NO-independent stimulators of soluble guanylate cyclase
Institute of Medicinal Chemistry, Pharma Research Centre, Bayer AG, Wuppertal, FRG
Bioorg Med Chem Lett 11:781-4. 2001
..Several pyrazolopyridinylpyrimidines are shown to relax aortic rings and revealed a long-lasting blood pressure lowering effect in rats after oral application...
- Modulating the hypoxia-inducible factor signaling pathway as a therapeutic modality to regulate retinal angiogenesis
Research Department, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia
Exp Eye Res 89:700-17. 2009
- Human trabecular meshwork cell volume decrease by NO-independent soluble guanylate cyclase activators YC-1 and BAY-58-2667 involves the BKCa ion channel
William M Dismuke
Department of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville, Florida 32610, USA
Invest Ophthalmol Vis Sci 50:3353-9. 2009
..This study investigated the effects of the nitric oxide (NO)-independent activators of soluble guanylate cyclase (sGC), YC-1, and BAY-58-2667 on TM cell volume and the signal transduction pathways and ion channel involved...
- [Os(IV)Cl(5)(Hazole)](-) complexes: synthesis, structure, spectroscopic properties, and antiproliferative activity
Gabriel E Büchel
University of Vienna, Institute of Inorganic Chemistry, Austria
Inorg Chem 48:10737-47. 2009
..Replacement of azolium cations by sodium had significant effects; cytotoxicity increased in the case of the pyrazole system from 3 (A549) to the 5.5-fold (CH1)...
- Pleiotropic effects of YC-1 selectively inhibit pathological retinal neovascularization and promote physiological revascularization in a mouse model of oxygen-induced retinopathy
Research Department, King Khaled Eye Specialist Hospital, Aruba Street, P O Box 7191, Riyadh 11462, Kingdom of Saudi Arabia
Mol Pharmacol 77:348-67. 2010
..The pleiotropic effects of YC-1 allude to its possible use as a promising therapeutic iNOS inhibitor candidate for the treatment of retinal neovascularization...
- Pharmacokinetic-pharmacodynamic modeling of tumor growth inhibition and biomarker modulation by the novel phosphatidylinositol 3-kinase inhibitor GDC-0941
Departments of Drug Metabolism and Pharmacokinetics, Genentech Inc, 1 DNA Way, South San Francisco, CA 94080, USA
Drug Metab Dispos 38:1436-42. 2010
- Stable expression of HIF-1alpha in tubular epithelial cells promotes interstitial fibrosis
First Department of Internal Medicine, Nara Medical University, 840 Shijo, Kashihara, Nara 634 8522, Japan
Am J Physiol Renal Physiol 295:F1023-9. 2008
..In conclusion, HIF-1alpha appears to be a critical contributor to the progression of renal fibrosis and could be a useful target for its treatment...
- YC-1 induces S cell cycle arrest and apoptosis by activating checkpoint kinases
Department of Pharmacology, Seoul National University College of Medicine, Seoul, South Korea
Cancer Res 66:6345-52. 2006
..These results imply that YC-1 does not promote the regrowth of hypoxic tumors because of its cell cycle arrest effect. Furthermore, YC-1 may induce the combined anticancer effects of HIF-1alpha inhibition and cell growth inhibition...
- YC-1: a potential anticancer drug targeting hypoxia-inducible factor 1
Department of Pharmacology, BK21 Human Life Sciences, Seoul National University College of Medicine, Seoul, Korea
J Natl Cancer Inst 95:516-25. 2003
..YC-1 has the potential to become the first antiangiogenic anticancer agent to target HIF-1 alpha...
- Inhibition of hypoxia-induced increase of blood-brain barrier permeability by YC-1 through the antagonism of HIF-1alpha accumulation and VEGF expression
Wei Lan Yeh
Department of Pharmacology, College of Medicine, National Taiwan University, 1, Sec 1, Jen Ai Road, Taipei, Taiwan
Mol Pharmacol 72:440-9. 2007
..Taken together, these results indicate that YC-1 may inhibit HIF-1alpha accumulation and VEGF production, which in turn protect BBB from injury caused by hypoxia...
- A domain responsible for HIF-1alpha degradation by YC-1, a novel anticancer agent
Department of Pharmacology, Seoul National University College of Medicine, Chongno-gu, Seoul 110-799, Korea
Int J Oncol 29:255-60. 2006
..However, their binding to HIF-1alpha was not affected by YC-1, suggesting that they are not involved in the YC-1 action. It is also suggested that YC-1 targets a novel pathway regulating HIF-1alpha stability...
- N-4-Pyrimidinyl-1H-indazol-4-amine inhibitors of Lck: indazoles as phenol isosteres with improved pharmacokinetics
GlaxoSmithKline R and D, Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK
Bioorg Med Chem Lett 17:4363-8. 2007
..Replacement of this substituent by 4-amino(5-methyl-1H-indazole) yielded compounds with comparable enzyme potency and improved pharmacokinetic properties...
- Adenine nucleotide translocator mediates the mitochondrial membrane permeabilization induced by lonidamine, arsenite and CD437
A S Belzacq
CNRS-UMR6022, , BP 20529, , France
Oncogene 20:7579-87. 2001
..These results indicate that ANT is a target of lonidamine, arsenite, and CD437 and unravel an unexpected heterogeneity in the mode of action of these three compounds...
- Amelioration of rat adjuvant arthritis by therapeutic treatment with bindarit, an inhibitor of MCP-1 and TNF-alpha production
Immunopharmacology Lab, ACRAF SpA Angelini Ricerche, Rome, Italy
Inflamm Res 51:252-8. 2002
..This study was designed to evaluate therapeutic effects of bindarit, an indazolic derivative able to inhibit monocyte chemoattractant protein-1 (MCP-1) production, in adjuvant induced arthritis in rats...
- Hypoxia-inducible factor-1 inhibition in combination with temozolomide treatment exhibits robust antitumor efficacy in vivo
Cancer Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, Illinois 60064, USA
Clin Cancer Res 12:4747-54. 2006
..In addition, our results also show that the RNA interference-based inducible knockdown model can be a valuable platform for further evaluation of the combination treatment of other cancer therapeutics with HIF-1 inhibition...
- Activators of soluble guanylate cyclase for the treatment of male erectile dysfunction
J D Brioni
Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, Illinois 60064, USA
Int J Impot Res 14:8-14. 2002
..This type of sGC activators represent a new class of compounds with a different pharmacological profile in comparison to the classical NO-donors and they could be beneficial for the treatment of male erectile dysfunction...
- Involvement of nitric oxide-soluble guanylyl cyclase pathway in the control of maximal dentate gyrus activation in the rat
Dipartimento di Medicina Sperimentale, Sezione di Fisiologia Umana G. Pagano, , Palermo, Italy
J Neural Transm 113:1855-61. 2006
..Our results indicate that the nitrergic neurotransmission exerts a modulatory role in the proneness to the epileptogenic phenomena through the activation of sGC metabolic pathway...
- Changes in nitric oxide synthesis and epileptic activity in the contralateral hippocampus of rats following intrahippocampal kainate injection
Department of Neurosurgery, Yamaguchi University School of Medicine 1144, Kogushi Ube, Yamaguchi 755-8505, Japan
Epilepsia 42:13-20. 2001
..CONCLUSIONS: The results suggest that remote seizure activity caused by the transneuronal spread of kainate-induced discharges may be related to NO derived from neuronal NOS...
- NO-independent regulatory site on soluble guanylate cyclase
J P Stasch
Pharma Research Center, Bayer AG, Aprather Wey 18a, D 42096 Wuppertal, Germany
Nature 410:212-5. 2001
..This results in antiplatelet activity, a strong decrease in blood pressure and an increase in survival in a low-NO rat model of hypertension, and as such may offer an approach for treating cardiovascular diseases...
- Impact of the anti-inflammatory agent bindarit on the chemokinome: selective inhibition of the monocyte chemotactic proteins
Istituto Clinico Humanitas IRCCS, Rozzano, Italy
Eur Cytokine Netw 19:119-22. 2008
..Here we report on the use of inhibition of synthesis as a potentially viable and selective approach to modify the chemokine system...
- The discharge of subthalamic neurons is modulated by inhibiting the nitric oxide synthase in the rat
Dipartimento di Medicina Sperimentale Sezione di Fisiologia umana, Universita degli Studi di Palermo, Corso Tukory, 129, Palermo 90134, Italy
Neurosci Lett 396:252-6. 2006
..We hypothesize that nitric oxide neurotransmission could exert a tonic modulatory influence upon spontaneously discharging subthalamic neurons, with a prevalent excitatory effect...
- ABT-869, a multi-targeted tyrosine kinase inhibitor, in combination with rapamycin is effective for subcutaneous hepatocellular carcinoma xenograft
Viraj J Jasinghe
Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, 5 Lower Kent Ridge Road, Singapore 119074, Singapore
J Hepatol 49:985-97. 2008
..Receptor tyrosine kinase inhibitors (RTKIs) and mTOR inhibitors are potential novel anticancer therapies for HCC. We hypothesized that combination targeted on distinctive signal pathways would provide synergistic therapeutics...
- Human soluble guanylate cyclase: functional expression and revised isoenzyme family
Department of Pharmacology and Toxicology, Julius Maximilians University, 9 Versbacher St, D 97078 Wurzburg, Germany
Biochem J 335:51-7. 1998
..Having access to the human key enzyme of NO signalling will now permit the study of novel sGC-modulating compounds with therapeutic potential...
- Increased neuronal nitric oxide synthase (nNOS) activity triggers picrotoxin-induced seizures in rats and evidence for participation of nNOS mechanism in the action of antiepileptic drugs
Department of Pharmacology and Environmental Toxicology, Dr ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani, 600 113, Chennai, India
Brain Res 979:85-97. 2003
..The results of the present study provide evidence for a trigger role of neuronally produced NO in epileptogenesis induced by PCT and the participation of nNOS inhibitory mechanisms in the action of AEDs...
- 7-Nitroindazole potentiates the anticonvulsant action of some second-generation antiepileptic drugs in the mouse maximal electroshock-induced seizure model
J J Luszczki
Department of Pathophysiology, Medical University of Lublin, Lublin, Poland
J Neural Transm 113:1157-68. 2006
- Treatment with bindarit, a blocker of MCP-1 synthesis, protects mice against acute pancreatitis
Dept of Pharmacology, National Univ of Singapore, Faculty of Medicine, Bldg MD2, 18 Medical Dr, Singapore 117597
Am J Physiol Gastrointest Liver Physiol 288:G1259-65. 2005
- Discovery of N-(4-(3-amino-1H-indazol-4-yl)phenyl)-N'-(2-fluoro-5-methylphenyl)urea (ABT-869), a 3-aminoindazole-based orally active multitargeted receptor tyrosine kinase inhibitor
Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, Illinois 60064 6100, USA
J Med Chem 50:1584-97. 2007
..In particular, compound 17p (ABT-869) was found to possess favorable pharmacokinetic profiles across different species and display significant tumor growth inhibition in multiple preclinical animal models...
- Axitinib treatment in patients with cytokine-refractory metastatic renal-cell cancer: a phase II study
Pitie Salpetriere Hospital, University of Paris, Paris, France
Lancet Oncol 8:975-84. 2007
..We aimed to assess the activity and safety of axitinib in patients with metastatic renal-cell cancer who had failed on previous cytokine-based treatment...
- Inhibitory effect of YC-1 on the hypoxic induction of erythropoietin and vascular endothelial growth factor in Hep3B cells
Y S Chun
Department of Pharmacology and Heart Research Institute, BK21 Human Life Sciences, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, 110-799, Seoul, South Korea
Biochem Pharmacol 61:947-54. 2001
..This observation implies that the inhibitory effects of YC-1 on hypoxic responses can be developed to suppress EPO-overproduction by tumor cells and tumor angiogenesis...
- Contributions of nitric oxide synthase isozymes to exhaled nitric oxide and hypoxic pulmonary vasoconstriction in rabbit lungs
David J Vaughan
Department of Pediatrics, Children's Hospital and Regional Medical Center, Seattle 98105, USA
Am J Physiol Lung Cell Mol Physiol 284:L834-43. 2003
..Our findings show virtually all exhaled NO in the rabbit lung is produced by eNOS, which is present throughout the airways, alveoli, and vessels. Both vascular and epithelial-derived NO modulate HPV...
- Synthesis and biological evaluation of novel pyrazoles and indazoles as activators of the nitric oxide receptor, soluble guanylate cyclase
D L Selwood
Biological and Medicinal Chemistry and Molecular and Cellular Biology, The Wolfson Institute for Biomedical Research, University College London, The Cruciform Building, Gower Street, London WC1E 6BT, UK
J Med Chem 44:78-93. 2001
..Furthermore 32 has an excellent selectivity profile notably showing no significant inhibition of phosphodiesterases or nitric oxide synthases...
- Inhibition of phosphorylation of the colony-stimulating factor-1 receptor (c-Fms) tyrosine kinase in transfected cells by ABT-869 and other tyrosine kinase inhibitors
Cancer Discovery Research R47J, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064 6121, USA
Mol Cancer Ther 5:1007-13. 2006
..These results show the use of a cell-based assay to confirm the inhibitory activity of lead compounds and drug candidates, such as ABT-869, against the CSF-1R protein in situ...
- YC-1 activation of human soluble guanylyl cyclase has both heme-dependent and heme-independent components
Department of Integrative Biology and Pharmacology, Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX 77030, USA
Proc Natl Acad Sci U S A 98:12938-42. 2001
..These findings indicate that YC-1 activation of sGC can occur independently of heme, but that activation is substantially increased when the heme moiety is present in the enzyme...
- In vivo activity of ABT-869, a multi-target kinase inhibitor, against acute myeloid leukemia with wild-type FLT3 receptor
Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
Leuk Res 32:1091-100. 2008
..ABT-869 also reduced the leukemia burden and prolonged survival. Our study supports the rationale for clinically testing an anti-angiogenesis agent in AML with wild-type FLT3...
- Purified soluble guanylyl cyclase expressed in a baculovirus/Sf9 system: stimulation by YC-1, nitric oxide, and carbon monoxide
DLR Institute of Aerospace Medicine, Cologne, Germany
J Mol Med (Berl) 77:14-23. 1999
..The described method should help to facilitate the investigation of the new therapeutic principle of NO-independent guanylyl cyclase activators...
- Interaction of nitric oxide, 20-HETE, and EETs during functional hyperemia in whisker barrel cortex
Dept of Anesthesiology and Critical Care Medicine, The Johns Hopkins Medical Institutions, 600 North Wolfe St Blalock 1404, Baltimore, MD 21287 4961, USA
Am J Physiol Heart Circ Physiol 295:H619-31. 2008
..With the chronic loss of neuronal NOS in mice, other mechanisms apparently suppress 20-HETE synthesis or signaling...
- Effects of 7-nitroindazole and N-nitro-l-arginine methyl ester on changes in cerebral blood flow and nitric oxide production preceding development of hyperbaric oxygen-induced seizures in rats
Department of Anesthesiology and Resuscitology, Okayama University Medical School, 2 5 1 Shikata cho, Okayama 700 8558, Japan
Neurosci Lett 382:206-10. 2005
..These findings suggest that neuronal NOS is the main mediator of NO production associated with increase in CBF leading to the appearance of electrical discharge during HBO(2) exposure...
- Dynamic association of nitric oxide downstream signaling molecules with endothelial caveolin-1 in rat aorta
A Elizabeth Linder
Medical College of Georgia, Department of Physiology CA 3101, 1120 Fifteenth St, Augusta, GA 30912 3000, USA
J Pharmacol Exp Ther 314:9-15. 2005
..In summary, our results provide evidence of compartmentalization of sGC, PKG, and PKA in endothelial caveolae contributing to NO signaling cascade, giving new insights by which the endothelium mediates vascular smooth muscle relaxation...
- Baclofen and NOS inhibitors interact to evoke synergistic hypothermia in rats
Scott M Rawls
Department of Pharmaceutical Sciences, Temple University School of Pharmacy, 3307 N Broad Street, Philadelphia, PA 19140, USA
Life Sci 78:669-72. 2006
..In a context broader than thermoregulation, NO production and transmission may play an important role in baclofen pharmacology...
- Maternal lead exposure produces long-term enhancement of dopaminergic reactivity in rat offspring
Department of Pharmacology, Medical University of Silesia, 41 808, Zabrze, Poland
Neurochem Res 32:1791-8. 2007
- Neuronal nitric oxide synthase and ischemia-induced neurogenesis
Buck Institute for Age Research, Novato, California 94945, USA
J Cereb Blood Flow Metab 25:485-92. 2005
..Selective inhibition of neuronal NO synthase may have the potential to both reduce infarct size and enhance neurogenesis in stroke...
- Role of neuronal nitric oxide synthase in response to hypertonic saline loading in rats
, Facultad de Medicina, University of Granada, Granada, Spain
Acta Physiol Scand 182:389-95. 2004
..Finally, it is concluded that nNOS participates in the homeostatic cardiovascular and renal response to hypertonic saline loading by attenuating the blood pressure increase and hypernatremia, and facilitating natriuresis...
- The role of nitric oxide on contractile impairment during endotoxemia in rat diaphragm muscle
Department of Pharmacology, Faculty of Medicine, Hacettepe University, Ankara 06100, Turkey
Eur J Pharmacol 505:177-86. 2004
..4) NO does not substantially modulate neuromuscular transmission in normal and endotoxemic rats...
- Participation of the GABA/benzodiazepine receptor and the NO-cyclicGMP pathway in the "antinociceptive-like effects" of diazepam
Departamento de Farmacobiologia, Centro de Investigación y de Estudios Avanzados Sede Sur, Calz de los Tenorios 235, Col Granjas Coapa, C P 14330, Mexico D F, Mexico
Pharmacol Biochem Behav 91:128-33. 2008
..These results suggest that the GABA/benzodiazepine receptor and the NO-cGMP pathway participate in the "antinociceptive-like effect" of diazepam...
- Sensory nitrergic meningeal vasodilatation and non-nitrergic plasma extravasation in anaesthesized rats
Department of Pharmacology and Pharmacotherapy, University of Debrecen, Nagyerdei krt 98, Debrecen H 4032, Hungary
Eur J Pharmacol 497:293-9. 2004
..This neurogenic oedema formation was not inhibited by neither L-NNA nor 3Br-7NI. It is concluded that neural nitrergic mechanisms are involved in the meningeal vasodilatation evoked by electrical stimulation of the trigeminal ganglion...
- Early diabetes as a model for testing the regulation of juxtaglomerular NOS I
Scott C Thomson
Department of Medicine, Division of Nephrology Hypertension, University of California and Veterans Affairs San Diego Health Care System, San Diego, CA 92161, USA
Am J Physiol Renal Physiol 287:F732-8. 2004
..In conclusion, normally, salt delivered to the macula densa (MD) exerts immediate control over MD NOS I activity. In diabetes, there is ongoing overactivity of NOS I that is not regulated by MD salt...
- Endothelial nitric oxide modulates perivascular sensory neurotransmission in the rat isolated mesenteric arterial bed
School of Biomedical Sciences, University of Nottingham Medical School, Queen s Medical Centre, Nottingham NG7 2UH
Br J Pharmacol 137:19-28. 2002
..The source of NO is the vascular endothelium...
- Involvement of nitric oxide pathway in the acute anticonvulsant effect of melatonin in mice
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box 13145-784, Tehran, Iran
Epilepsy Res 68:103-13. 2006
..The present data show an anticonvulsant effect for melatonin in i.v. PTZ seizure paradigm, which may be mediated via NO/L-arginine pathway by constitutively expressed NOS...
- Renal tissue NO and intrarenal haemodynamics during experimental variations of NO content in anaesthetised rats
M Grzelec Mojzesowicz
Laboratory of Renal and Body Fluid Physiology, M Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland
J Physiol Pharmacol 58:149-63. 2007
..Since inhibition of nNOS decreased medullary NO by 80% and MBF by 20% only, this isoform has probably minor role in the maintenance of medullary perfusion...
- A potentiating effect of endogenous NO in the physiologic secretion from airway submucosal glands
Department of Infectious and Respiratory Diseases, Tohoku University School of Medicine, 1 1, Seiryo machi, Aoba ku, Sendai 980 8574, Japan
Am J Respir Cell Mol Biol 37:357-65. 2007
..Therefore, due to NO, gland cells become more sensitive to calcium signaling and are able to maintain electrolyte secretion without desensitization...
- Mediation of glutamatergic receptors and nitric oxide on striatal dopamine release evoked by anatoxin-a. An in vivo microdialysis study
Department of Functional Biology and Health Sciences, Faculty of Biology, University of Vigo, Vigo Pontevedra, Spain
Eur J Pharmacol 548:90-8. 2006
..On the other hand, activation of NMDA receptors may elicit NO increased levels enhancing dopamine release...
- Intracerebroventricular administration of nitric oxide-sensitive guanylyl cyclase inhibitors induces catalepsy in mice
M B Echeverry
Department MEF Physiology, FORP, University of Sao Paulo, Av Café S No, 14040 904, Ribeirao Preto, SP, Brazil
Psychopharmacology (Berl) 194:271-8. 2007
..Although several effects mediated by NO involve the activation of soluble guanylyl cyclase (sGC), the transduction mechanism of the catalepsy-inducing effect of NO has not yet been investigated...
- Modulatory effects of nitric oxide-active drugs on the anticonvulsant activity of lamotrigine in an experimental model of partial complex epilepsy in the rat
Dipartimento di Medicina Sperimentale, Sezione di Fisiologia umana G, Pagano, Universita degli Studi di Palermo, C so Tukory, Palermo, Italy
BMC Neurosci 8:47. 2007
..The epileptic activity of the dentate gyrus was obtained through the repetitive stimulation of the angular bundle and maximal dentate gyrus activation latency, duration and post-stimulus afterdischarge duration were evaluated...
- Anxiolytic effects induced by inhibition of the nitric oxide-cGMP pathway in the rat dorsal hippocampus
P C M Spolidório
Department MEF Physiology, School of Odontology, Campus USP Ribeirão Preto, 14049 904, Ribeirao Preto, SP, Brazil
Psychopharmacology (Berl) 195:183-92. 2007
..Conflicting results have been reported regarding the role of the nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) pathway in the hippocampus on anxiety modulation...
- The role of nitric oxide in the anticonvulsant effects of pyridoxine on penicillin-induced epileptiform activity in rats
Department of Physiology, Faculty of Medicine, University of Gaziantep, Gaziantep, Turkey
Epilepsy Res 76:49-59. 2007
- Nitric oxide is involved in the memory facilitation induced by spermidine in rats
Gustavo Petri Guerra
Departamento de Quimica, Centro de Ciencias Naturais e Exatas, Laboratorio de Neurotoxicidade e Psicofarmacologia, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil
Psychopharmacology (Berl) 186:150-8. 2006
..Spermidine (SPD) is an endogenous polyamine that modulates N-methyl-D: -aspartate receptor functions, which has been reported to facilitate memory formation...
- Nitric oxide synthase mediates delta opioid receptor-induced hypothermia in rats
Scott M Rawls
Department of Pharmaceutical Sciences, Temple University School of Pharmacy, 3307 North Broad Street, Philadelphia, PA, 19140, USA
Eur J Pharmacol 536:109-12. 2006
..p.). Experiments revealed that L-NAME (1 mg/rat, i.c.v.) attenuated SNC-80-induced hypothermia. The present data demonstrate that central NO production is necessary for delta opioid receptor-induced hypothermia...
- Nitric oxide-mediated anxiolytic-like and antidepressant-like effects in animal models of anxiety and depression
State University of Maringa, Department of Pharmacology, Maringa, Brazil
Pharmacol Biochem Behav 88:247-55. 2008
..These results show that interference with NO-mediated neurotransmission in the DRN induced significant and complex motor and emotional effects. Further studies are needed to elucidate the mechanisms involved in these effects...
- The nitric oxide-cyclic GMP-protein kinase G-K+ channel pathway participates in the antiallodynic effect of spinal gabapentin
, , Calzada de los Tenorios 235, Colonia Granjas Coapa, 14330, , DF, Mexico
Eur J Pharmacol 531:87-95. 2006
..Data suggest that gabapentin-induced spinal antiallodynia could be due to activation of the NO-cyclic GMP-PKG-K+ channel pathway...
- Hypoxia induces complex I inhibition and ultrastructural damage by increasing mitochondrial nitric oxide in developing CNS
Institute of Cell Biology and Neuroscience Prof E De Robertis, School of Medicine, University of Buenos Aires, Paraguay 2155, 1121 Buenos Aires, Argentina
Eur J Neurosci 27:123-31. 2008
..In conclusion, we show here for the first time that hypoxia induces NO-dependent complex I inhibition and ultrastructural damage by increasing mitochondrial NO in the developing brain...
- Adrenomedullin in the rostral ventrolateral medulla increases arterial pressure and heart rate: roles of glutamate and nitric oxide
Dept. of Cell Biology and Center for Neuroscience, Faculty of Medicine and Dentistry, Univ. of Alberta, Edmonton, AB, Canada
Am J Physiol Regul Integr Comp Physiol 287:R729-34. 2004
..These effects are mediated by glutamate via both NMDA and non-NMDA receptors. NO, derived from neuronal NO synthase, also contributes to the ADM-induced vasopressor effects via a soluble guanylyl cyclase-associated signaling pathway...
- Interactions between nitric oxide and renal nerves in the excretion of a saline load in obese Zucker rats
Department of Physiology, Medical School, University of Birmingham, Birmingham B15 2TT
Clin Sci (Lond) 101:275-83. 2001
..NO, possibly generated by endothelial NO synthase, exerts its effects in obese rats through a renal-nerve-independent mechanism, while the effect of NO generated by inducible NO synthase requires intact renal innervation...
- Glutamate and NO mediation of the pressor response to 5-HT3 receptor stimulation in the nucleus tractus solitarii
INSERM U 288, CHU Pitie Salpetriere, 91 blvd de l Hôpital, 75634 Paris Cedex 13, France
Neuroreport 13:837-41. 2002
..These data suggest that ionotropic glutamate receptors and the associated NO/cGMP transduction mechanism contribute downstream to the pressor effect elicited by 5-HT3 receptor stimulation in the NTS...
- Inhibition of nitric oxide synthase influences the activity of striatal neurons in the rat
Dipartimento di Medicina Sperimentale, Sezione di Fisiologia Umana, , Corso Tukory, 129-90134 Palermo, Italy
Neurosci Lett 325:179-82. 2002
..We hypothesize that NO neurotransmission could exert a tonic inhibitory influence upon sporadically discharging striatal neurons, which are presumably striatal output neurons...
- Cyclooxygenase-2 products compensate for inhibition of nitric oxide regulation of renal perfusion
William H Beierwaltes
Hypertension and Vascular Research Division, Henry Ford Hospital, Detroit, Michigan 48202 2689, USA
Am J Physiol Renal Physiol 283:F68-72. 2002
..Acute NOS inhibition unmasked renal vasoconstriction with COX-2 inhibition, suggesting that the influence of COX-2-derived vasodilator eicosanoids is exaggerated to maintain renal perfusion, compensating for the acute loss of NO...
- Reduction of cGMP and nitric oxide has antidepressant-like effects in the forced swimming test in rats
Ida Louise Heiberg
Institute for Basic Psychiatric Research, Department of Biological Psychiatry, Skovagervej 2, DK-8240 Risskov, Denmark
Behav Brain Res 134:479-84. 2002
..These findings suggest that the NO-sGC-cGMP pathway may play an important role in the mediation of the behavioural effect in the FST without influence on motor activity...
- Downregulation of nNOS and synthesis of PGs associated with endotoxin-induced delay in gastric emptying
Unidad Mixta de Investigacion, Hospital Clínico Universidad de Valencia, Spain
Am J Physiol Gastrointest Liver Physiol 283:G1360-7. 2002
..Our results suggest that downregulation of nNOS in the antrum pylorus of the stomach and synthesis of prostaglandins mediate the delay in gastric emptying of a solid nutrient meal induced by endotoxin...
- Severe cerebral blood flow reduction inhibits nitric oxide synthesis
Department of Neurosurgery, Clinical Neuroscience, Yamaguchi University School of Medicine, Ube, Japan
J Neurotrauma 19:1105-16. 2002
..It is also suggested that NO synthesis during ischemia is closely related to CBF, and that severe CBF reduction may inhibit NO synthesis...
- Compensatory role of NO in cerebral circulation of piglets chronically treated with indomethacin
Laboratory for Research in Neonatal Physiology, Department of Physiology, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA
Am J Physiol Regul Integr Comp Physiol 282:R400-10. 2002
..These data suggest that chronic inhibition of cyclooxygenase can increase the contribution of NO to cerebrovascular circulatory control in piglets...
- Stimulation of perivascular nitric oxide synthesis by oxygen
Stephen R Thom
Department of Emergency Medicine, University of Pennsylvania Medical Center, Philadelphia 19104, USA
Am J Physiol Heart Circ Physiol 284:H1230-9. 2003
..NO associated with hemoglobin. These findings highlight the complexity of oxidative stress responses and may help explain some of the dose responses associated with therapeutic applications of hyperbaric oxygen...
- Inhibition by ebselen on nitric oxide mediated relaxations in the rat anococcygeus muscle
Division of Biosciences, School of Medical Sciences, RMIT University, GPO Box 71, Bundoora, Victoria 3083, Australia
Eur J Pharmacol 462:161-8. 2003
..Ebselen does not appear to directly interact with NO, but it may inhibit NO release from nitrosothiols by a thiol- and/or copper-dependent mechanism...
- Facilitatory role of NO in neural norepinephrine release in the rat kidney
Laboratory of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan
Am J Physiol Regul Integr Comp Physiol 282:R1436-42. 2002
- Nitric oxide modulation of neurally induced proximal tubular fluid reabsorption in the rat
Xiao Chun Wu
Department of Physiology, The Medical School, Birmingham, United Kingdom
Hypertension 39:790-3. 2002
..Moreover, the findings have revealed that the presence of NO is necessary to ensure that renal nerves can stimulate fluid reabsorption by the proximal tubules, requiring NO generated from both nNOS and iNOS...
- Neuroprotective effect of sigma(1)-receptor ligand 4-phenyl-1-(4-phenylbutyl) piperidine (PPBP) is linked to reduced neuronal nitric oxide production
Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Stroke 32:1613-20. 2001
..Neuroprotective effects of PPBP are lost when nNOS is not present or is inhibited; therefore, PPBP likely acts upstream from NO generation and its subsequent neurotoxicity...
- Anesthesia alters NO-mediated functional hyperemia
R J Gerrits
Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA
Brain Res 907:20-6. 2001
..Taken together, these data do not support a primary role for NO in rat WBC functional hyperemia and suggest that previous reports of inhibition may have been secondary to the anesthesia employed...
- Inhibition of neuronal nitric oxide synthase ameliorates renal hyperfiltration in streptozotocin-induced diabetic rat
First Department of Internal Medicine and Kidney Center, University of Occupational and Environmental Health School of Medicine, Kitakyushu, Japan
J Lab Clin Med 138:177-85. 2001
- The nNOS/cGMP signal transducing system is involved in the cardiovascular responses induced by activation of NMDA receptors in the rostral ventrolateral medulla of cats
W C Wu
Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan
Neurosci Lett 310:121-4. 2001
..These findings suggest that NO is involved in the NMDA-induced cardiovascular responses in the RVLM...
- Nitric oxide- and oxygen-derived free radical generation from control and lipopolysaccharide-treated rat polymorphonuclear leukocyte
Pharmacology Division, Central Drug Research Institute, Lucknow 226001, India
Nitric Oxide 5:482-93. 2001
..The results obtained thus indicate that augmentation of free radical generation from rat PMNs following LPS treatment appears to be regulated by NO and MPO...
- Nitric oxide regulation of lingual blood flow in the rat
Z V Roberts
Department of Cell Biology, University of Oklahoma College of Medicine, Oklahoma City, Oklahoma 73190, USA
Nitric Oxide 5:271-7. 2001
- Effects of nitric oxide synthase inhibitors on the discriminative stimulus effects of cocaine in rats
S L Collins
Laboratory of Behavioral Neuroscience, Department of Psychology, Boston University, 64 Cummington Street, Boston, Massachusetts, USA
Psychopharmacology (Berl) 154:261-73. 2001
..CONCLUSIONS: These findings suggest that L-NAME and 7-NI may increase the potency of cocaine and other indirect DA agonists through a central mechanism whereby DA neurotransmission is directly enhanced by NOS inhibition...
- Regulatory role of nitric oxide over hippocampal 5-HT release in vivo
Department of Pharmacology, The School of Pharmacy, London, UK
Naunyn Schmiedebergs Arch Pharmacol 363:302-6. 2001
..It may be that the recorded changes in 5-HT release are secondary to changes in the release of amino acid transmitters which we have previously found to be dependent on the prevailing extracellular NO concentration...
- Effects of intracerebroventricular administration of 7-nitroindazole on tolerance to ethanol
Departamento de Farmacologia, , Universidade Federal de Santa Catarina, Rua Ferreira Lima 82, , SC, Brazil
Brain Res Bull 57:165-70. 2002
..c.v. injection of 7-NI also blocked the development of tolerance to the hypothermic effect of ethanol. These results support the hypothesis that nNOS-derived NO participates in the development of rapid tolerance to ethanol...
- Homocysteine-induced brain lipid peroxidation: effects of NMDA receptor blockade, antioxidant treatment, and nitric oxide synthase inhibition
Departamento de Genetica, , S.S.A. Insurgentes Sur # 3877, , 14269,
Neurotox Res 5:237-43. 2003
..These results show that submillimolar concentrations of HCY can induce oxidative injury to nerve terminals, and this effect involves NMDAr stimulation, NOS activation, and associated free radicals formation...