Thomas R Miller

Summary

Affiliation: Abbott Laboratories
Country: USA

Publications

  1. doi Spinal microglial activation in rat models of neuropathic and osteoarthritic pain: an autoradiographic study using [3H]PK11195
    T R Miller
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, USA
    Eur J Pain 17:692-703. 2013
  2. doi A robust and high-capacity [(35)S]GTPgammaS binding assay for determining antagonist and inverse agonist pharmacological parameters of histamine H(3) receptor ligands
    Thomas R Miller
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064 6125, USA
    Assay Drug Dev Technol 6:339-49. 2008
  3. pmc Use of the H3 receptor antagonist radioligand [3H]-A-349821 to reveal in vivo receptor occupancy of cognition enhancing H3 receptor antagonists
    T R Miller
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA
    Br J Pharmacol 157:139-49. 2009
  4. ncbi Synthesis, potency, and in vivo profiles of quinoline containing histamine H3 receptor inverse agonists
    Robert J Altenbach
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, Illinois 60064 6123, USA
    J Med Chem 50:5439-48. 2007
  5. ncbi Pharmacological and behavioral properties of A-349821, a selective and potent human histamine H3 receptor antagonist
    Timothy A Esbenshade
    Abbott Laboratories, Global Pharmaceutical Research Division, Department of Neuroscience Research, Abbott Park, IL 60064, USA
    Biochem Pharmacol 68:933-45. 2004
  6. ncbi Pharmacological properties of ABT-239 [4-(2-{2-[(2R)-2-Methylpyrrolidinyl]ethyl}-benzofuran-5-yl)benzonitrile]: I. Potent and selective histamine H3 receptor antagonist with drug-like properties
    Timothy A Esbenshade
    Neuroscience Research, Abbott Laboratories, R4MN, AP9A, 100 Abbott Park Road, Abbott Park, IL 60064, USA
    J Pharmacol Exp Ther 313:165-75. 2005
  7. ncbi Structure-activity relationships of non-imidazole H(3) receptor ligands. Part 2: binding preference for D-amino acids motifs
    Ramin Faghih
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064 6123, USA
    Bioorg Med Chem Lett 12:2035-7. 2002
  8. doi cis-4-(Piperazin-1-yl)-5,6,7a,8,9,10,11,11a-octahydrobenzofuro[2,3-h]quinazolin-2-amine (A-987306), a new histamine H4R antagonist that blocks pain responses against carrageenan-induced hyperalgesia
    Huaqing Liu
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, Illinois 60064 6100, USA
    J Med Chem 51:7094-8. 2008
  9. ncbi G protein-dependent pharmacology of histamine H3 receptor ligands: evidence for heterogeneous active state receptor conformations
    Kathleen M Krueger
    Neurosciences Research, Abbott Laboratories, Global Pharmaceutical Research and Development, Abbott Park, IL 60064 6125, USA
    J Pharmacol Exp Ther 314:271-81. 2005
  10. doi Rotationally constrained 2,4-diamino-5,6-disubstituted pyrimidines: a new class of histamine H4 receptor antagonists with improved druglikeness and in vivo efficacy in pain and inflammation models
    Marlon D Cowart
    Department of Neuroscience Research, Abbott Laboratories, Abbott Park, Illinois 60064 6123, USA
    J Med Chem 51:6547-57. 2008

Detail Information

Publications35

  1. doi Spinal microglial activation in rat models of neuropathic and osteoarthritic pain: an autoradiographic study using [3H]PK11195
    T R Miller
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, USA
    Eur J Pain 17:692-703. 2013
    ..Following pronociceptive stimulation, activated microglia exhibit increased expression of the peripheral benzodiazepine receptor (PBR)/translocator protein 18 kDa (TSPO)...
  2. doi A robust and high-capacity [(35)S]GTPgammaS binding assay for determining antagonist and inverse agonist pharmacological parameters of histamine H(3) receptor ligands
    Thomas R Miller
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064 6125, USA
    Assay Drug Dev Technol 6:339-49. 2008
    ..These robust and reliable [(35)S]GTPgammaS binding assays have become one of the important tools in our pharmacological analysis and development of novel histamine H(3) receptor antagonists/inverse agonists...
  3. pmc Use of the H3 receptor antagonist radioligand [3H]-A-349821 to reveal in vivo receptor occupancy of cognition enhancing H3 receptor antagonists
    T R Miller
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA
    Br J Pharmacol 157:139-49. 2009
    ..This model was established as an alternative to ex vivo binding methods, for relating antagonist H3 receptor occupancy to blood levels and efficacy in preclinical models...
  4. ncbi Synthesis, potency, and in vivo profiles of quinoline containing histamine H3 receptor inverse agonists
    Robert J Altenbach
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, Illinois 60064 6123, USA
    J Med Chem 50:5439-48. 2007
    ..Further studies on the pharmaceutic properties of this series of quinolines discovered a potential problem with photochemical instability, an issue which contributed to the discontinuation of this series from further development...
  5. ncbi Pharmacological and behavioral properties of A-349821, a selective and potent human histamine H3 receptor antagonist
    Timothy A Esbenshade
    Abbott Laboratories, Global Pharmaceutical Research Division, Department of Neuroscience Research, Abbott Park, IL 60064, USA
    Biochem Pharmacol 68:933-45. 2004
    ..Thus, A-349821 is a novel, selective non-imidazole H3 antagonist/inverse agonist with balanced high potency across species and favorable cognition enhancing effects in rats...
  6. ncbi Pharmacological properties of ABT-239 [4-(2-{2-[(2R)-2-Methylpyrrolidinyl]ethyl}-benzofuran-5-yl)benzonitrile]: I. Potent and selective histamine H3 receptor antagonist with drug-like properties
    Timothy A Esbenshade
    Neuroscience Research, Abbott Laboratories, R4MN, AP9A, 100 Abbott Park Road, Abbott Park, IL 60064, USA
    J Pharmacol Exp Ther 313:165-75. 2005
    ..Thus, ABT-239 is a selective, nonimidazole H3 receptor antagonist/inverse agonist with similar high potency in both human and rat and favorable drug-like properties...
  7. ncbi Structure-activity relationships of non-imidazole H(3) receptor ligands. Part 2: binding preference for D-amino acids motifs
    Ramin Faghih
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064 6123, USA
    Bioorg Med Chem Lett 12:2035-7. 2002
    ..Structure-activity relationship studies on novel non-imidazole, D-amino acid containing ligands of histamine 3 receptors are presented. A-304121 is a D-alanine piperazine amide with high affinity at the rat H(3) receptor...
  8. doi cis-4-(Piperazin-1-yl)-5,6,7a,8,9,10,11,11a-octahydrobenzofuro[2,3-h]quinazolin-2-amine (A-987306), a new histamine H4R antagonist that blocks pain responses against carrageenan-induced hyperalgesia
    Huaqing Liu
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, Illinois 60064 6100, USA
    J Med Chem 51:7094-8. 2008
    ..Most interesting was the high potency and efficacy of this compound in blocking pain responses, where it showed an ED(50) of 42 mumol/kg (ip) in a rat post-carrageenan thermal hyperalgesia model of inflammatory pain...
  9. ncbi G protein-dependent pharmacology of histamine H3 receptor ligands: evidence for heterogeneous active state receptor conformations
    Kathleen M Krueger
    Neurosciences Research, Abbott Laboratories, Global Pharmaceutical Research and Development, Abbott Park, IL 60064 6125, USA
    J Pharmacol Exp Ther 314:271-81. 2005
    ....
  10. doi Rotationally constrained 2,4-diamino-5,6-disubstituted pyrimidines: a new class of histamine H4 receptor antagonists with improved druglikeness and in vivo efficacy in pain and inflammation models
    Marlon D Cowart
    Department of Neuroscience Research, Abbott Laboratories, Abbott Park, Illinois 60064 6123, USA
    J Med Chem 51:6547-57. 2008
    ..6 and 1.6 h, oral bioavailability of 37% and 90%) with anti-inflammatory activity (ED 50 = 37 micromol/kg, mouse) and efficacy in pain models (thermal hyperalgesia, ED 50 = 72 micromol/kg, rat)...
  11. doi The alkaloid conessine and analogues as potent histamine H3 receptor antagonists
    Chen Zhao
    Department of Neuroscience Research, Global Pharmaceutical Research Division, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, Illinois 60064 6123, USA
    J Med Chem 51:5423-30. 2008
    ..One optimized analogue (13c) was examined in detail and was found to be efficacious in animal behavioral model of cognition...
  12. doi Cloning and characterization of the monkey histamine H3 receptor isoforms
    Marina I Strakhova
    Neuroscience Research, Global Pharmaceutical Research Division, Abbott Laboratories, R 4MN, AP9A, 100 Abbott Park Road, Abbott Park, Illinois 60064, USA
    Eur J Pharmacol 601:8-15. 2008
    ....
  13. pmc Detection of multiple H3 receptor affinity states utilizing [3H]A-349821, a novel, selective, non-imidazole histamine H3 receptor inverse agonist radioligand
    David G Witte
    Neuroscience Research, Dept R4MN, Global Pharmaceutical Research Division, Abbott Laboratories, Bldg AP9A 2, 100 Abbott Park Road, Abbott Park, IL 60064, USA
    Br J Pharmacol 148:657-70. 2006
    ..3H]A-349821 competition studies showed significant differences in the proportions and potencies of high- and low-affinity sites across species, providing new information about the fundamental pharmacological nature of H3 receptors...
  14. doi Design of a new histamine H3 receptor antagonist chemotype: (3aR,6aR)-5-alkyl-1-aryl-octahydropyrrolo[3,4-b]pyrroles, synthesis, and structure-activity relationships
    Chen Zhao
    Department of Neuroscience Research, Global Pharmaceutical Research Division, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, Illinois 60064 6123, USA
    J Med Chem 52:4640-9. 2009
    ..54 nM, rat H3 K(i) of 4.57 nM, and excellent pharmacokinetics (PK) profile in rats (oral bioavailability of 39% and t(1/2) of 2.4 h)...
  15. ncbi Evidence for tolerance following repeated dosing in rats with ciproxifan, but not with A-304121
    Jia Bao Pan
    Neuroscience Research, Abbott Laboratories, 100 Abbott Road, Abbott Park, IL 60064 6125, USA
    Life Sci 79:1366-79. 2006
    ..The implications for potential long-term treatment with H(3) receptor antagonists in CNS disorders such as ADHD are discussed...
  16. doi Rigidified 2-aminopyrimidines as histamine H4 receptor antagonists: effects of substitution about the rigidifying ring
    John R Koenig
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064 6100, USA
    Bioorg Med Chem Lett 20:1900-4. 2010
    ..In addition, representative compounds are able to completely block itch responses when dosed ip in a mouse model of H(4)-agonist induced scratching, thus demonstrating their activities as H(4)R antagonists...
  17. ncbi Novel heterocyclic-substituted benzofuran histamine H3 receptor antagonists: in vitro properties, drug-likeness, and behavioral activity
    Marlon Cowart
    GPRD_AP9a 216, Department of Neuroscience Research, Abbott Laboratories, Abbott Park, IL 60064 6123, USA
    Biochem Pharmacol 73:1243-55. 2007
    ..v. administration (t(1/2) in rat of 2.9h, 1.7h in dog, 1.8h in monkey), suggesting poor human pharmacokinetics, the data overall indicated that A-688057 has an excellent profile for use as a pharmacological tool compound...
  18. ncbi Two novel and selective nonimidazole histamine H3 receptor antagonists A-304121 and A-317920: I. In vitro pharmacological effects
    Timothy A Esbenshade
    Neuroscience Research, Global Pharmaceutical Research Division, Abbott Laboratories, R4MN, AP9A, 100 Abbott Park Road, Abbott Park, IL 60064, USA
    J Pharmacol Exp Ther 305:887-96. 2003
    ..7 and 7.0) than are the imidazole antagonists. These novel and selective piperazine amides represent useful leads for the development of H3R antagonist therapeutic agents...
  19. ncbi Synthesis and SAR of 5-amino- and 5-(aminomethyl)benzofuran histamine H3 receptor antagonists with improved potency
    Minghua Sun
    Neuroscience Research, Global Pharmaceutical Research Division, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, Illinois 60064 6123, USA
    J Med Chem 48:6482-90. 2005
    ..The synthesis, SAR of the H3 binding affinities, in vitro assay for phospholipidosis, and pharmacokinetic properties of the new compounds are described...
  20. doi Structure-activity studies on a series of a 2-aminopyrimidine-containing histamine H4 receptor ligands
    Robert J Altenbach
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, Illinois 60064 6100, USA
    J Med Chem 51:6571-80. 2008
    ....
  21. ncbi In vitro optimization of structure activity relationships of analogues of A-331440 combining radioligand receptor binding assays and micronucleus assays of potential antiobesity histamine H3 receptor antagonists
    Arthur A Hancock
    Department of Exploratory Neurobiology, Global Pharmaceuticals Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064 6125, USA
    Basic Clin Pharmacol Toxicol 95:144-52. 2004
    ..Preliminary findings with one of these examples, A-417022, in a mouse model of obesity are presented...
  22. doi Pharmacological properties and procognitive effects of ABT-288, a potent and selective histamine H3 receptor antagonist
    Timothy A Esbenshade
    Global Pharmaceutical Research Division, Abbott Laboratories, Abbott Park, IL 60064, USA
    J Pharmacol Exp Ther 343:233-45. 2012
    ..Thus, ABT-288 is a selective H(3)R antagonist with broad procognitive efficacy in rodents and excellent drug-like properties that support its advancement to the clinical area...
  23. ncbi 4-[6-(2-Aminoethyl)naphthalen-2-yl]benzonitriles are potent histamine H3 receptor antagonists with high CNS penetration
    Lawrence A Black
    Neuroscience Research, GPRD, Abbott Laboratories, Abbott Park, IL 60064, USA
    Bioorg Med Chem Lett 17:1443-6. 2007
    ..The SAR of the tertiary amine moiety is similar to that reported for the benzofuran series, with analogs bearing a 2-methylpyrrolidine substituent possessing the greatest rat and human H3 receptor binding affinities...
  24. ncbi Differential activation of dual signaling responses by human H1 and H2 histamine receptors
    Timothy A Esbenshade
    Neuroscience Research, Global Pharmaceutical Research Division, Abbott Laboratories, Abbott Park, Illinois 60064, USA
    J Recept Signal Transduct Res 23:17-31. 2003
    ..86 and 4.82, respectively). These studies demonstrate a markedly different potency for activation of multiple signaling pathways by H1- and H2-HRs that may contribute to the selectivity of histamine responses in vivo...
  25. ncbi In vitro SAR of pyrrolidine-containing histamine H3 receptor antagonists: trends across multiple chemical series
    Diana L Nersesian
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064, USA
    Bioorg Med Chem Lett 18:355-9. 2008
    ..The libraries were constructed with a variety of low molecular weight pyrrolidines, selected from (R)-2-methylpyrrolidine, (S)-2-methylpyrrolidine, and pyrrolidine...
  26. ncbi Structure-activity relationships of non-imidazole H(3) receptor ligands. Part 3: 5-Substituted 3-phenyl-1,2,4-oxadiazoles as potent antagonists
    Gregory A Gfesser
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064, USA
    Bioorg Med Chem Lett 14:673-6. 2004
    ..Compound 14bb is a potent antagonist of both the rat cortical and human clone receptors, and is demonstrated to act functionally as an antagonist in an in vivo mouse dipsogenia model...
  27. doi H4 receptor antagonism exhibits anti-nociceptive effects in inflammatory and neuropathic pain models in rats
    Gin C Hsieh
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, Illinois 60064, USA
    Pharmacol Biochem Behav 95:41-50. 2010
    ..Our results demonstrate that selective blockade of H(4) receptors in vivo produces significant anti-nociception in animal models of inflammatory and neuropathic pain...
  28. doi In vitro studies on a class of quinoline containing histamine H3 antagonists
    Huaqing Liu
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064 6123, USA
    Bioorg Med Chem Lett 20:3295-300. 2010
    ..These analogs were synthesized via the Friedlander quinoline synthesis between an aminoaldehyde intermediate and a methyl ketone allowing for a wide diversity of substituents at the 2-position of the quinoline ring...
  29. ncbi 2-[4-(3,4-Dimethylphenyl)piperazin-1-ylmethyl]-1H benzoimidazole (A-381393), a selective dopamine D4 receptor antagonist
    Masaki Nakane
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA
    Neuropharmacology 49:112-21. 2005
    ..A-381393 inhibited penile erection induced by the selective D4 agonist PD168077 in conscious rats. Thus, A-381393 is a novel selective D4 antagonist that will enhance the ability to study dopamine D4 receptors both in vitro and in vivo...
  30. ncbi Structure-activity relationships of non-imidazole H(3) receptor ligands. Part 1
    Ramin Faghih
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064 6123, USA
    Bioorg Med Chem Lett 12:2031-4. 2002
    ..A high throughput screening lead, A-923, was further elaborated in a systematic manner to clarify a pharmacophore for this class of aryloxyalkyl piperazine based compounds...
  31. pmc Pharmacological characterization of a 1,4-dihydropyridine analogue, 9-(3,4-dichlorophenyl)-3,3,6,6-tetramethyl-3,4,6,7,9,10-hexahydro-1,8(2H,5H)-acridinedione (A-184209) as a novelK(ATP) channel inhibitor
    Murali Gopalakrishnan
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, Illinois, IL 60064, U S A
    Br J Pharmacol 138:393-9. 2003
    ....
  32. ncbi Synthesis and structure-activity studies on N-[5-(1H-imidazol-4-yl)-5,6,7,8-tetrahydro-1-naphthalenyl]methanesulfonamide, an imidazole-containing alpha(1A)-adrenoceptor agonist
    Robert J Altenbach
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064 6123, USA
    J Med Chem 47:3220-35. 2004
    ..However, the data also support a prominent role of the alpha(1A)-AR subtype in the control of MAP...
  33. ncbi An 80-amino acid deletion in the third intracellular loop of a naturally occurring human histamine H3 isoform confers pharmacological differences and constitutive activity
    Gerold Bongers
    Leiden Amsterdam Center for Drug Research, Department of Medicinal Chemistry, Vrije Universiteit Amsterdam, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands
    J Pharmacol Exp Ther 323:888-98. 2007
    ....
  34. ncbi Regulation of nociceptin/orphaninFQ secretion by immune cells and functional modulation of interleukin-2
    Thomas R Miller
    Department of Anatomy, University of Bristol, Southwell Street, Bristol, UK
    Peptides 28:2243-52. 2007
    ..In summary we have shown how a variety of stimuli relevant to inflammation can regulate endogenous N/OFQ secretion by splenocytes in vitro. We also suggest that N/OFQ may promote anti-inflammatory actions via suppression of IL-2 in vivo...
  35. ncbi Effect of subclinical status in functional limitation and disability on adverse health outcomes 3 years later
    Fredric D Wolinsky
    Iowa City VAMC, Iowa, USA
    J Gerontol A Biol Sci Med Sci 62:101-6. 2007
    ..This article examines the effect of self-reported, baseline subclinical status (i.e., independent but adaptive performance) for functional limitation and disability on adverse health outcomes...