Lee A Dawson

Summary

Affiliation: GlaxoSmithKline Research and Development
Country: USA

Publications

  1. ncbi request reprint In vitro and in vivo characterization of the non-peptide NK3 receptor antagonist SB-223412 (talnetant): potential therapeutic utility in the treatment of schizophrenia
    Lee A Dawson
    Psychiatry Centre of Excellence for Drug Discovery, GlaxoSmithKline, Essex, UK
    Neuropsychopharmacology 33:1642-52. 2008
  2. ncbi request reprint 5-HT1 receptor augmentation strategies as enhanced efficacy: therapeutics for psychiatric disorders
    Lee A Dawson
    Psychiatry CEDD, GlaxoSmithKline, Harlow, UK
    Curr Top Med Chem 8:1008-23. 2008
  3. ncbi request reprint Characterisation of the selective 5-HT1B receptor antagonist SB-616234-A (1-[6-(cis-3,5-dimethylpiperazin-1-yl)-2,3-dihydro-5-methoxyindol-1-yl]-1-[2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methanone hydrochloride): in vivo neurochemical a
    Lee A Dawson
    Psychiatry Centre of Excellence for Drug Discovery, GlaxoSmithKline, New Frontiers Science Park North, 3rd Avenue, Harlow, Essex CM19 5AW, UK
    Neuropharmacology 50:975-83. 2006
  4. ncbi request reprint SB-649915-B, a novel 5-HT1A/B autoreceptor antagonist and serotonin reuptake inhibitor, is anxiolytic and displays fast onset activity in the rat high light social interaction test
    Kathryn R Starr
    Schizophrenia and Bipolar Research, Psychiatry Centre of Excellence in Drug Discovery, GlaxoSmithKline, New Frontiers Science Park, Essex CM19 5AW, UK
    Neuropsychopharmacology 32:2163-72. 2007
  5. ncbi request reprint SB-616234-A (1-[6-(cis-3,5-dimethylpiperazin-1-yl)-2,3-dihydro-5-methoxyindol-1-yl]-1-[2'methyl-4'-(5-methyl-1,2,3-oxadiazol-3-yl)biphenyl-4-yl]methanone hydrochloride): a novel, potent and selective 5-HT1B receptor antagonist
    Claire Scott
    Department of Biology, Psychiatry Centre of Excellence for Drug Discovery, GlaxoSmithKline, Harlow, Essex, UK
    Neuropharmacology 50:984-90. 2006
  6. doi request reprint In vitro and in vivo comparison of two non-peptide tachykinin NK3 receptor antagonists: Improvements in efficacy achieved through enhanced brain penetration or altered pharmacological characteristics
    Lee A Dawson
    Neurosciences Centre of Excellence for Drug Discovery, GlaxoSmithKline, New Frontiers Science Park, Harlow, Essex, UK
    Eur J Pharmacol 627:106-14. 2010
  7. ncbi request reprint Simultaneous blockade of 5-HT1A/B receptors and 5-HT transporters results in acute increases in extracellular 5-HT in both rats and guinea pigs: in vivo characterization of the novel 5-HT1A/B receptor antagonist/5-HT transport inhibitor SB-649915-B
    Zoe A Hughes
    Psychiatry Centre of Excellence for Drug Discovery, GlaxoSmithKline, New Frontiers Science Park North, Harlow, Essex, CM19 5AW, UK
    Psychopharmacology (Berl) 192:121-33. 2007
  8. ncbi request reprint Neurochemical evaluation of the novel 5-HT1A receptor partial agonist/serotonin reuptake inhibitor, vilazodone
    Zoe A Hughes
    Neuropharmacology Research, Psychiatry CEDD, Glaxo Smith Kline, New Frontiers Science Park, Third Avenue, Harlow, Essex, CM19 5AW, UK
    Eur J Pharmacol 510:49-57. 2005
  9. doi request reprint Augmentation of antipsychotic-induced neurochemical changes by the NK3 receptor antagonist talnetant (SB-223412)
    Raúl de la Flor
    GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, UK
    Neuropharmacology 56:342-9. 2009
  10. ncbi request reprint SB-699551-A (3-cyclopentyl-N-[2-(dimethylamino)ethyl]-N-[(4'-{[(2-phenylethyl)amino]methyl}-4-biphenylyl)methyl]propanamide dihydrochloride), a novel 5-ht5A receptor-selective antagonist, enhances 5-HT neuronal function: Evidence for an autoreceptor role
    David R Thomas
    Psychiatry Centre of Excellence for Drug Discovery, GlaxoSmithKline, New Frontiers Science Park North, Harlow, Essex, UK
    Neuropharmacology 51:566-77. 2006

Detail Information

Publications37

  1. ncbi request reprint In vitro and in vivo characterization of the non-peptide NK3 receptor antagonist SB-223412 (talnetant): potential therapeutic utility in the treatment of schizophrenia
    Lee A Dawson
    Psychiatry Centre of Excellence for Drug Discovery, GlaxoSmithKline, Essex, UK
    Neuropsychopharmacology 33:1642-52. 2008
    ....
  2. ncbi request reprint 5-HT1 receptor augmentation strategies as enhanced efficacy: therapeutics for psychiatric disorders
    Lee A Dawson
    Psychiatry CEDD, GlaxoSmithKline, Harlow, UK
    Curr Top Med Chem 8:1008-23. 2008
    ..Here we will review the rationale behind the various augmentation strategies adopted and the progress made in identifying novel therapeutics for conditions such as depression and anxiety disorders...
  3. ncbi request reprint Characterisation of the selective 5-HT1B receptor antagonist SB-616234-A (1-[6-(cis-3,5-dimethylpiperazin-1-yl)-2,3-dihydro-5-methoxyindol-1-yl]-1-[2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methanone hydrochloride): in vivo neurochemical a
    Lee A Dawson
    Psychiatry Centre of Excellence for Drug Discovery, GlaxoSmithKline, New Frontiers Science Park North, 3rd Avenue, Harlow, Essex CM19 5AW, UK
    Neuropharmacology 50:975-83. 2006
    ..Taken together these data suggest that SB-616234-A may have therapeutic efficacy in the treatment of affective disorders...
  4. ncbi request reprint SB-649915-B, a novel 5-HT1A/B autoreceptor antagonist and serotonin reuptake inhibitor, is anxiolytic and displays fast onset activity in the rat high light social interaction test
    Kathryn R Starr
    Schizophrenia and Bipolar Research, Psychiatry Centre of Excellence in Drug Discovery, GlaxoSmithKline, New Frontiers Science Park, Essex CM19 5AW, UK
    Neuropsychopharmacology 32:2163-72. 2007
    ..In conclusion, SB-649915-B is acutely anxiolytic and reduces the latency to onset of anxiolytic behavior compared to paroxetine in the SI model...
  5. ncbi request reprint SB-616234-A (1-[6-(cis-3,5-dimethylpiperazin-1-yl)-2,3-dihydro-5-methoxyindol-1-yl]-1-[2'methyl-4'-(5-methyl-1,2,3-oxadiazol-3-yl)biphenyl-4-yl]methanone hydrochloride): a novel, potent and selective 5-HT1B receptor antagonist
    Claire Scott
    Department of Biology, Psychiatry Centre of Excellence for Drug Discovery, GlaxoSmithKline, Harlow, Essex, UK
    Neuropharmacology 50:984-90. 2006
    ..83+/-0.39 mg kg(-1) p.o. Taken together these data suggest that SB-616234-A is a potent and selective 5-HT(1B) autoreceptor antagonist that occupies central 5-HT1B receptors in vivo following oral administration...
  6. doi request reprint In vitro and in vivo comparison of two non-peptide tachykinin NK3 receptor antagonists: Improvements in efficacy achieved through enhanced brain penetration or altered pharmacological characteristics
    Lee A Dawson
    Neurosciences Centre of Excellence for Drug Discovery, GlaxoSmithKline, New Frontiers Science Park, Harlow, Essex, UK
    Eur J Pharmacol 627:106-14. 2010
    ..Taken together, these in vitro and in vivo characterisations of the tachykinin NK(3) receptor antagonists GSK172981 and GSK256471 support their potential utility in the treatment of schizophrenia...
  7. ncbi request reprint Simultaneous blockade of 5-HT1A/B receptors and 5-HT transporters results in acute increases in extracellular 5-HT in both rats and guinea pigs: in vivo characterization of the novel 5-HT1A/B receptor antagonist/5-HT transport inhibitor SB-649915-B
    Zoe A Hughes
    Psychiatry Centre of Excellence for Drug Discovery, GlaxoSmithKline, New Frontiers Science Park North, Harlow, Essex, CM19 5AW, UK
    Psychopharmacology (Berl) 192:121-33. 2007
    ..The delay in onset and treatment resistance of subpopulations of depressed patients to conventional serotonin reuptake inhibitors has lead to new drug development strategies to produce agents with improved antidepressant efficacy...
  8. ncbi request reprint Neurochemical evaluation of the novel 5-HT1A receptor partial agonist/serotonin reuptake inhibitor, vilazodone
    Zoe A Hughes
    Neuropharmacology Research, Psychiatry CEDD, Glaxo Smith Kline, New Frontiers Science Park, Third Avenue, Harlow, Essex, CM19 5AW, UK
    Eur J Pharmacol 510:49-57. 2005
    ..This profile was similar to that seen with a 5-HT1A receptor antagonist plus an SSRI but in contrast to 8-OH-DPAT either alone or in combination with paroxetine...
  9. doi request reprint Augmentation of antipsychotic-induced neurochemical changes by the NK3 receptor antagonist talnetant (SB-223412)
    Raúl de la Flor
    GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, UK
    Neuropharmacology 56:342-9. 2009
    ..These data suggest that addition of talnetant to antipsychotic drugs may facilitate monoaminergic neurotransmission and hence potentially improve their clinical efficacy...
  10. ncbi request reprint SB-699551-A (3-cyclopentyl-N-[2-(dimethylamino)ethyl]-N-[(4'-{[(2-phenylethyl)amino]methyl}-4-biphenylyl)methyl]propanamide dihydrochloride), a novel 5-ht5A receptor-selective antagonist, enhances 5-HT neuronal function: Evidence for an autoreceptor role
    David R Thomas
    Psychiatry Centre of Excellence for Drug Discovery, GlaxoSmithKline, New Frontiers Science Park North, Harlow, Essex, UK
    Neuropharmacology 51:566-77. 2006
    ..3 mg/kg s.c.), SB-699551-A (0.3, 1 or 3 mg/kg s.c.) produced a significant increase in extracellular 5-HT levels. These studies provide evidence for an autoreceptor role for the 5-ht5A receptor in guinea pig brain...
  11. doi request reprint Preclinical investigations into the antipsychotic potential of the novel histamine H3 receptor antagonist GSK207040
    Eric Southam
    GlaxoSmithKline, New Frontiers Science Park North, Third Avenue, Harlow, Essex, CM195AW, UK
    Psychopharmacology (Berl) 201:483-94. 2009
    ....
  12. ncbi request reprint Characterization of the potent 5-HT(1A/B) receptor antagonist and serotonin reuptake inhibitor SB-649915: preclinical evidence for hastened onset of antidepressant/anxiolytic efficacy
    Jeannette M Watson
    Psychiatry Centre of Excellence for Drug Discovery, GlaxoSmithKline, New Frontiers Science Park, Harlow, Essex, UK
    CNS Drug Rev 13:206-23. 2007
    ..In summary, SB-649915 is a novel, potent 5-HT1A/1B autoreceptor antagonist, and 5-HT reuptake inhibitor. This particular pharmacological profile provides a novel mechanism that could offer fast-acting antidepressant activity...
  13. ncbi request reprint SB-399885 is a potent, selective 5-HT6 receptor antagonist with cognitive enhancing properties in aged rat water maze and novel object recognition models
    Warren D Hirst
    Neurology and GI Centre of Excellence for Drug Discovery, GlaxoSmithKline, Harlow, Essex, CM19 5AW, UK
    Eur J Pharmacol 553:109-19. 2006
    ..These studies provide further support for the potential therapeutic utility of 5-HT(6) receptor antagonists in disorders characterised by cognitive deficits such as Alzheimer's disease and schizophrenia...
  14. ncbi request reprint Vilazodone: a 5-HT1A receptor agonist/serotonin transporter inhibitor for the treatment of affective disorders
    Lee A Dawson
    Neurosciences Centre of Excellence for Drug Discovery, GlaxoSmithKline, Harlow, Essex, UK
    CNS Neurosci Ther 15:107-17. 2009
    ..Ongoing clinical evaluations will hopefully reveal whether the founding hypothesis was valid and if vilazodone will produce a more rapid onset of antidepressant efficacy...
  15. ncbi request reprint Neurochemical changes in LPA1 receptor deficient mice--a putative model of schizophrenia
    Claire Roberts
    Psychiatry Centre of Excellence for Drug Discovery, GlaxoSmithKline, New Frontiers Science Park, Third Avenue, CM19 5AW, Harlow, Essex, UK
    Neurochem Res 30:371-7. 2005
    ..In summary, these data demonstrate that the lpa1 mutation produces a number of changes in neurotransmitters that have been associated with a schizophrenic-like pathology...
  16. doi request reprint Selective dopamine D4 receptor agonist (A-412997) improves cognitive performance and stimulates motor activity without influencing reward-related behaviour in rat
    Marie L Woolley
    Neurosciences Centre of Excellence for Drug Discovery, GlaxoSmithKline plc, New Frontiers Science Park, Harlow, Essex, UK
    Behav Pharmacol 19:765-76. 2008
    ....
  17. ncbi request reprint The effect of clozapine on extracellular dopamine levels in the shell subregion of the rat nucleus accumbens is reversed following chronic administration: comparison with a selective 5-HT(2C) receptor antagonist
    Claire S Shilliam
    Department of Neuropharmacology, Psychiatry Centre of Excellence for Drug Discovery, GlaxoSmithKline, Harlow, UK
    Neuropsychopharmacology 30:372-80. 2005
    ..However, since SB-243213 had no effect on DA levels in the NAcc, it is likely that 5-HT(2C) receptor antagonism alone is not the mechanism by which clozapine exerts is actions...
  18. doi request reprint Effects of N-acetylaspartylglutamate (NAAG) at group II mGluRs and NMDAR
    Anne Cécile Fricker
    Psychiatry Discovery Technology Group, GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow, Essex CM195AW, United Kingdom
    Neuropharmacology 56:1060-7. 2009
    ..Taken together, these findings do not support a rationale for targeting NAALADase and increasing extracellular NAAG levels as a therapeutic strategy for the treatment of schizophrenia...
  19. doi request reprint Attenuation of amphetamine-induced activity by the non-selective muscarinic receptor agonist, xanomeline, is absent in muscarinic M4 receptor knockout mice and attenuated in muscarinic M1 receptor knockout mice
    Marie L Woolley
    Neurosciences CEDD, GlaxoSmithKline plc, New Frontiers Science Park, Harlow, Essex, England
    Eur J Pharmacol 603:147-9. 2009
    ..This supports the hypothesis that activation of M(4), and to a lesser extent M(1) muscarinic acetylcholine receptors, may represent a potential target for the treatment of psychosis seen in schizophrenia...
  20. doi request reprint Evidence for antimanic efficacy of glycogen synthase kinase-3 (GSK3) inhibitors in a strain-specific model of acute mania
    Mikhail Kalinichev
    Neurosciences Centre of Excellence for Drug Discovery, GlaxoSmithKline, New Frontiers Science Park, Harlow, Essex, UK
    Int J Neuropsychopharmacol 14:1051-67. 2011
    ..These data support the predictive validity of the model for the acute manic phase of BD and may have utility as an in-vivo model for identifying novel antimanic therapeutics...
  21. doi request reprint Development and application of a liquid chromatography/tandem mass spectrometric assay for measurement of N-acetylaspartate, N-acetylaspartylglutamate and glutamate in brain slice superfusates and tissue extracts
    Ajit J Shah
    Neurosciences Centre of Excellence for Drug Discovery, GlaxoSmithKline plc, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, UK
    J Chromatogr B Analyt Technol Biomed Life Sci 876:153-8. 2008
    ..The assay was also used for measurement of the distribution of Glu, NAA and NAAG in different regions of the rat brain...
  22. ncbi request reprint Therapeutic utility of NK3 receptor antagonists for the treatment of schizophrenia
    Lee A Dawson
    Neurosciences CEDD, GlaxoSmithKline, New Frontiers Science Park, Harlow, Essex
    Curr Pharm Des 16:344-57. 2010
    ..Finally we will summarize the available clinical information on those compounds which have progressed into patient populations and evaluate their potential therapeutic utility, and the future of the NK(3) receptor target...
  23. doi request reprint New quinoline NK3 receptor antagonists with CNS activity
    Paul W Smith
    Medicinal Chemistry, Neuroscience CEDD GlaxoSmithKline Research and Development, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, UK
    Bioorg Med Chem Lett 19:837-40. 2009
    ..Both 10 and 20 are high affinity, potent NK(3) receptor antagonists which despite having different degrees of CNS penetration produced excellent NK(3) receptor occupancy in an ex vivo binding study in gerbil cortex...
  24. ncbi request reprint Differential autoreceptor control of extracellular 5-HT in guinea pig and rat: species and regional differences
    Zoe A Hughes
    Neuropharmacology Research, Psychiatry Centre of Excellence for Drug Discovery, GlaxoSmithKline, New Frontiers Science Park North, Harlow, CM19 5AW, Essex, UK
    Psychopharmacology (Berl) 172:87-93. 2004
    ..Central 5-hydroxytryptamine (5-HT) release is regulated by inhibitory 5-HT autoreceptors, including 5-HT(1A) and 5-HT(1B) receptors...
  25. ncbi request reprint GSK189254, a novel H3 receptor antagonist that binds to histamine H3 receptors in Alzheimer's disease brain and improves cognitive performance in preclinical models
    Andrew D Medhurst
    Neurology and GI Centre of Excellence for Drug Discovery, GlaxoSmithKline, Third Ave, Harlow, Essex, CM19 5AW, UK
    J Pharmacol Exp Ther 321:1032-45. 2007
    ..3 and 1 mg/kg p.o.), and attentional set shift (1 mg/kg p.o.). These data suggest that GSK189254 may have therapeutic potential for the symptomatic treatment of dementia in Alzheimer's disease and other cognitive disorders...
  26. ncbi request reprint Potentiation of amphetamine-induced changes in dopamine and 5-HT by a 5-HT(6) receptor antagonist
    Lee A Dawson
    Neuroscience Research, Wyeth Ayerst, Princeton, NJ, USA
    Brain Res Bull 59:513-21. 2003
    ..This is the first direct neurochemical evidence that the 5-HT(6) receptor may have modulatory influences on both DA and 5-HT systems in the rat striatum...
  27. ncbi request reprint 5-HT6 receptor antagonist SB-271046 enhances extracellular levels of monoamines in the rat medial prefrontal cortex
    Laurent P Lacroix
    Centre of Excellence for Drug Discovery in Psychiatry, Department of Biology, GlaxoSmithKline Pharmaceuticals, 37135 Verona, Italy, and Harlow, CM19 5AW, UK
    Synapse 51:158-64. 2004
    ..These results further support the rationale for the use of 5-HT(6) receptor antagonists in the treatment of cognitive dysfunction associated with psychiatric diseases...
  28. ncbi request reprint BACE1 (beta-secretase) transgenic and knockout mice: identification of neurochemical deficits and behavioral changes
    Steve M Harrison
    Department of Comparative Genomics, GlaxoSmithKline, New Frontiers Science Park North, Third Avenue, Harlow, Essex CM19 5AW, UK
    Mol Cell Neurosci 24:646-55. 2003
    ..These results suggest an unexpected role for BACE1 in neurotransmission, perhaps through changes in amyloid precursor protein processing and Abeta levels...
  29. ncbi request reprint Neurokinin 3 (NK3) receptor modulators for the treatment of psychiatric disorders
    Paul W Smith
    Psychiatry Centre of Excellence in Drug Discovery, GlaxoSmithKline, Harlow, UK
    Recent Pat CNS Drug Discov 3:1-15. 2008
    ..In this article, the authors review the recent patent literature highlighting the various NK(3) receptor modulation strategies for potential therapeutic utility in psychiatric disease indications...
  30. ncbi request reprint High-performance liquid chromatography/tandem mass spectrometry assay for the rapid high sensitivity measurement of basal acetylcholine from microdialysates
    Mark E P Hows
    Computational Analytical and Structural Sciences, GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow, CM19 5AW, Essex, UK
    J Neurosci Methods 121:33-9. 2002
    ..Furthermore, separation conditions were modified to allow simultaneous measurement of ACh and the acetylcholine esterase inhibitor, neostigmine...
  31. ncbi request reprint Identification of a potent and selective 5-HT1B receptor antagonist
    Paul A Wyman
    Psychiatry CEDD, New Frontiers Science Park, GlaxoSmithKline, Third Avenue, Harlow, Essex CM19 5AW, UK
    Bioorg Med Chem Lett 15:4708-12. 2005
    ..This led to the identification of the selective 5-HT1B receptor antagonist SB-616234...
  32. ncbi request reprint Regulators of G-protein signaling 4: modulation of 5-HT1A-mediated neurotransmitter release in vivo
    Chad E Beyer
    Neuroscience Discovery Research, Wyeth Research, CN 8000, Princeton, NJ 08543 8000, USA
    Brain Res 1022:214-20. 2004
    ....
  33. ncbi request reprint WAY-163909 [(7bR,10aR)-1,2,3,4,8,9,10,10a-octahydro-7bH-cyclopenta-[b][1,4]diazepino[6,7,1hi]indole]: A novel 5-hydroxytryptamine 2C receptor-selective agonist with preclinical antipsychotic-like activity
    Karen L Marquis
    Discovery Neuroscience, Wyeth Research, CN 8000, Princeton, NJ 08543, USA
    J Pharmacol Exp Ther 320:486-96. 2007
    ..p.). Thus, the profile of the 5-HT2C selective receptor agonist WAY-163909 is similar to that of an atypical antipsychotic and additionally may have rapid onset properties...
  34. doi request reprint Correlating efficacy in rodent cognition models with in vivo 5-hydroxytryptamine1a receptor occupancy by a novel antagonist, (R)-N-(2-methyl-(4-indolyl-1-piperazinyl)ethyl)-N-(2-pyridinyl)-cyclohexane carboxamide (WAY-101405)
    Warren D Hirst
    Discovery Neuroscience, Wyeth Research, CN 8000, Princeton, NJ 08543, USA
    J Pharmacol Exp Ther 325:134-45. 2008
    ..These results further support the rationale for use of this compound class in the treatment of cognitive dysfunction associated with psychiatric and neurological conditions...
  35. ncbi request reprint Comparison of the effects of antidepressants on norepinephrine and serotonin concentrations in the rat frontal cortex: an in-vivo microdialysis study
    Chad E Beyer
    Neuroscience Discovery Research, Wyeth Research, Princeton, New Jersey 08543 8000, USA
    J Psychopharmacol 16:297-304. 2002
    ....
  36. ncbi request reprint Discovery of N1-(6-chloroimidazo[2,1-b][1,3]thiazole-5-sulfonyl)tryptamine as a potent, selective, and orally active 5-HT(6) receptor agonist
    Derek C Cole
    Chemical and Screening Sciences, Wyeth Research, 401 N Middletown Road, Pearl River, New York 10965, USA
    J Med Chem 50:5535-8. 2007
    ....
  37. ncbi request reprint Neuropharmacological profile of novel and selective 5-HT6 receptor agonists: WAY-181187 and WAY-208466
    Lee E Schechter
    Discovery Neuroscience, Wyeth Research, Princeton, NJ 08543 8000, USA
    Neuropsychopharmacology 33:1323-35. 2008
    ....