Prisca Honore

Summary

Affiliation: Abbott Laboratories
Country: USA

Publications

  1. ncbi request reprint A-740003 [N-(1-{[(cyanoimino)(5-quinolinylamino) methyl]amino}-2,2-dimethylpropyl)-2-(3,4-dimethoxyphenyl)acetamide], a novel and selective P2X7 receptor antagonist, dose-dependently reduces neuropathic pain in the rat
    Prisca Honore
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, Illinois 60064, USA
    J Pharmacol Exp Ther 319:1376-85. 2006
  2. ncbi request reprint TNP-ATP, a potent P2X3 receptor antagonist, blocks acetic acid-induced abdominal constriction in mice: comparison with reference analgesics
    Prisca Honore
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA
    Pain 96:99-105. 2002
  3. ncbi request reprint Analgesic profile of intrathecal P2X(3) antisense oligonucleotide treatment in chronic inflammatory and neuropathic pain states in rats
    Prisca Honore
    Abbott Laboratories, Neuroscience Research, Global Pharmaceutical Research and Development, 100 Abbott Park Road, Abbott Park, IL 60064, USA
    Pain 99:11-9. 2002
  4. ncbi request reprint A-425619 [1-isoquinolin-5-yl-3-(4-trifluoromethyl-benzyl)-urea], a novel transient receptor potential type V1 receptor antagonist, relieves pathophysiological pain associated with inflammation and tissue injury in rats
    Prisca Honore
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA
    J Pharmacol Exp Ther 314:410-21. 2005
  5. doi request reprint A-887826 is a structurally novel, potent and voltage-dependent Na(v)1.8 sodium channel blocker that attenuates neuropathic tactile allodynia in rats
    Xu Feng Zhang
    Neuroscience Research, Abbott Laboratories, 100 Abbott Park Rd, Abbott Park, IL 60064, USA
    Neuropharmacology 59:201-7. 2010
  6. ncbi request reprint Involvement of the TTX-resistant sodium channel Nav 1.8 in inflammatory and neuropathic, but not post-operative, pain states
    S K Joshi
    Abbott Laboratories, Neuroscience Research, Abbott Park, IL 60064, USA
    Pain 123:75-82. 2006
  7. pmc Effects of A-317491, a novel and selective P2X3/P2X2/3 receptor antagonist, on neuropathic, inflammatory and chemogenic nociception following intrathecal and intraplantar administration
    Steve McGaraughty
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, R4PM, AP9 1, 100 Abbott Park Road, Abbott Park, IL 60064 6118, USA
    Br J Pharmacol 140:1381-8. 2003
  8. pmc Endogenous opioid mechanisms partially mediate P2X3/P2X2/3-related antinociception in rat models of inflammatory and chemogenic pain but not neuropathic pain
    Steve McGaraughty
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, R4PM, AP9 1, 100 Abbott Park Road, Abbott Park, IL 60064, U S A
    Br J Pharmacol 146:180-8. 2005
  9. doi request reprint 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
  10. ncbi request reprint Additive antinociceptive effects of the selective Nav1.8 blocker A-803467 and selective TRPV1 antagonists in rat inflammatory and neuropathic pain models
    S K Joshi
    Abbott Laboratories, Neuroscience Research, Abbott Park, Illinois, USA
    J Pain 10:306-15. 2009

Detail Information

Publications70

  1. ncbi request reprint A-740003 [N-(1-{[(cyanoimino)(5-quinolinylamino) methyl]amino}-2,2-dimethylpropyl)-2-(3,4-dimethoxyphenyl)acetamide], a novel and selective P2X7 receptor antagonist, dose-dependently reduces neuropathic pain in the rat
    Prisca Honore
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, Illinois 60064, USA
    J Pharmacol Exp Ther 319:1376-85. 2006
    ..These data demonstrate that selective blockade of P2X(7) receptors in vivo produces significant antinociception in animal models of neuropathic and inflammatory pain...
  2. ncbi request reprint TNP-ATP, a potent P2X3 receptor antagonist, blocks acetic acid-induced abdominal constriction in mice: comparison with reference analgesics
    Prisca Honore
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA
    Pain 96:99-105. 2002
    ..Together, these results show that activation of P2X3 containing receptors plays a role in the transmission of inflammatory visceral pain...
  3. ncbi request reprint Analgesic profile of intrathecal P2X(3) antisense oligonucleotide treatment in chronic inflammatory and neuropathic pain states in rats
    Prisca Honore
    Abbott Laboratories, Neuroscience Research, Global Pharmaceutical Research and Development, 100 Abbott Park Road, Abbott Park, IL 60064, USA
    Pain 99:11-9. 2002
    ....
  4. ncbi request reprint A-425619 [1-isoquinolin-5-yl-3-(4-trifluoromethyl-benzyl)-urea], a novel transient receptor potential type V1 receptor antagonist, relieves pathophysiological pain associated with inflammation and tissue injury in rats
    Prisca Honore
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA
    J Pharmacol Exp Ther 314:410-21. 2005
    ..o.). Taken together, the present data indicate that A-425619, a potent and selective antagonist of TRPV1 receptors, effectively relieves acute and chronic inflammatory pain and postoperative pain...
  5. doi request reprint A-887826 is a structurally novel, potent and voltage-dependent Na(v)1.8 sodium channel blocker that attenuates neuropathic tactile allodynia in rats
    Xu Feng Zhang
    Neuroscience Research, Abbott Laboratories, 100 Abbott Park Rd, Abbott Park, IL 60064, USA
    Neuropharmacology 59:201-7. 2010
    ..The ability of this structurally novel Na(v)1.8 blocker to effectively reduce tactile allodynia in neuropathic rats further supports the role of Na(v)1.8 sodium channels in pathological pain states...
  6. ncbi request reprint Involvement of the TTX-resistant sodium channel Nav 1.8 in inflammatory and neuropathic, but not post-operative, pain states
    S K Joshi
    Abbott Laboratories, Neuroscience Research, Abbott Park, IL 60064, USA
    Pain 123:75-82. 2006
    ..6+/-6.2% effect, p<0.05 vs. MM). These data demonstrate a greater involvement of Nav 1.8 in frank nerve injury and inflammatory pain as compared to acute, post-operative or chemotherapy-induced neuropathic pain states...
  7. pmc Effects of A-317491, a novel and selective P2X3/P2X2/3 receptor antagonist, on neuropathic, inflammatory and chemogenic nociception following intrathecal and intraplantar administration
    Steve McGaraughty
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, R4PM, AP9 1, 100 Abbott Park Road, Abbott Park, IL 60064 6118, USA
    Br J Pharmacol 140:1381-8. 2003
    ..Intrathecal administration of A-317491 appears to be more effective than intraplantar administration to reduce tactile allodynia following peripheral nerve injury...
  8. pmc Endogenous opioid mechanisms partially mediate P2X3/P2X2/3-related antinociception in rat models of inflammatory and chemogenic pain but not neuropathic pain
    Steve McGaraughty
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, R4PM, AP9 1, 100 Abbott Park Road, Abbott Park, IL 60064, U S A
    Br J Pharmacol 146:180-8. 2005
    ..Taken together, these results indicate that antagonism of spinal P2X3/P2X2/3 receptors results in an indirect activation of the opioid system to alleviate inflammatory hyperalgesia and chemogenic nociception...
  9. doi request reprint 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...
  10. ncbi request reprint Additive antinociceptive effects of the selective Nav1.8 blocker A-803467 and selective TRPV1 antagonists in rat inflammatory and neuropathic pain models
    S K Joshi
    Abbott Laboratories, Neuroscience Research, Abbott Park, Illinois, USA
    J Pain 10:306-15. 2009
    ..Using such a combination strategy to produce analgesia may potentially provide an improved therapeutic separation from unwanted in vivo side effects associated with blockade of either Nav1.8 or TRPV1 alone...
  11. doi request reprint The antihyperalgesic activity of a selective P2X7 receptor antagonist, A-839977, is lost in IL-1alphabeta knockout mice
    Prisca Honore
    Abbott Laboratories, Neuroscience Research, Abbott Park, IL 60064, USA
    Behav Brain Res 204:77-81. 2009
    ....
  12. ncbi request reprint Analgesic activity of metabotropic glutamate receptor 1 antagonists on spontaneous post-operative pain in rats
    Chang Z Zhu
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064 3500, USA
    Eur J Pharmacol 580:314-21. 2008
    ....
  13. doi request reprint Tetrahydropyridine-4-carboxamides as novel, potent transient receptor potential vanilloid 1 (TRPV1) antagonists
    Brian S Brown
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Dept R4PM, AP10 207, 100 Abbott Park Road, Abbott Park, IL 60064 6100, USA
    Bioorg Med Chem 16:8516-25. 2008
    ..The SAR leading to the discovery of 6 is presented in this report...
  14. doi request reprint Structure-activity relationship studies on N'-aryl carbohydrazide P2X7 antagonists
    Derek W Nelson
    Abbott Laboratories, Neuroscience Research and Advanced Technology, Global Pharmaceutical Research and Development, Abbott Park, Illinois 60064 6101, USA
    J Med Chem 51:3030-4. 2008
    ..Compounds with potent antagonist function were evaluated in vivo using the zymosan-induced peritonitis model. A representative compound effectively attenuated mechanical allodynia in a rat model of neuropathic pain...
  15. doi request reprint Identification of (R)-1-(5-tert-butyl-2,3-dihydro-1H-inden-1-yl)-3-(1H-indazol-4-yl)urea (ABT-102) as a potent TRPV1 antagonist for pain management
    Arthur Gomtsyan
    Global Pharmaceutical Research and Development, Neuroscience Research, Abbott Laboratories, Abbott Park, IL 60064, USA
    J Med Chem 51:392-5. 2008
    ..Both the analgesic activity and drug-like properties of ( R)-7 support its advancement into clinical pain trials...
  16. ncbi request reprint Repeated dosing of ABT-102, a potent and selective TRPV1 antagonist, enhances TRPV1-mediated analgesic activity in rodents, but attenuates antagonist-induced hyperthermia
    Prisca Honore
    Abbott Laboratories, Abbott Park, IL 60064, USA
    Pain 142:27-35. 2009
    ..The analgesic efficacy of ABT-102 supports its advancement into clinical studies...
  17. doi request reprint Central pituitary adenylate cyclase 1 receptors modulate nociceptive behaviors in both inflammatory and neuropathic pain states
    Rachel Davis-Taber
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, Illinois 60064, USA
    J Pain 9:449-56. 2008
    ..These results further emphasize that at the level of the spinal cord, PAC(1)-R activation is pronociceptive...
  18. ncbi request reprint Contributions of central and peripheral TRPV1 receptors to mechanically evoked and spontaneous firing of spinal neurons in inflamed rats
    Steve McGaraughty
    Neuroscience Research, Abbott Laboratories, Abbott Park, IL 60064 6118, USA
    J Neurophysiol 100:3158-66. 2008
    ..Furthermore this study delineates the differential contribution of central and peripheral TRPV1 receptors to affect spontaneous or mechanically evoked firing of WDR neurons...
  19. doi request reprint 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...
  20. doi request reprint Discovery and biological evaluation of 5-aryl-2-furfuramides, potent and selective blockers of the Nav1.8 sodium channel with efficacy in models of neuropathic and inflammatory pain
    Michael E Kort
    Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064 6100, USA
    J Med Chem 51:407-16. 2008
    ..2, Nav1.5, Nav1.7) and human ether-a-go-go (hERG) channels. Following systemic administration, compounds 7 and 27 dose-dependently reduced neuropathic and inflammatory pain in experimental rodent models...
  21. ncbi request reprint In vitro structure-activity relationship and in vivo characterization of 1-(aryl)-3-(4-(amino)benzyl)urea transient receptor potential vanilloid 1 antagonists
    Richard J Perner
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, Illinois 60064, USA
    J Med Chem 50:3651-60. 2007
    ..Further optimization of 45 resulted in compound 58 with substantially improved microsome stability and oral bioavailability, as well as in vivo activity...
  22. pmc A-803467, a potent and selective Nav1.8 sodium channel blocker, attenuates neuropathic and inflammatory pain in the rat
    Michael F Jarvis
    Neuroscience Research, Abbott Laboratories, Abbott Park, IL 60064, USA
    Proc Natl Acad Sci U S A 104:8520-5. 2007
    ..These data demonstrate that acute and selective pharmacological blockade of Na(v)1.8 sodium channels in vivo produces significant antinociception in animal models of neuropathic and inflammatory pain...
  23. doi request reprint Discovery and biological evaluation of novel cyanoguanidine P2X(7) antagonists with analgesic activity in a rat model of neuropathic pain
    Arturo Perez-Medrano
    Abbott Laboratories, Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Park, Illinois 60064 6101, USA
    J Med Chem 52:3366-76. 2009
    ..These results suggest an important role of P2X(7) receptors in neuropathic pain and therefore a potential use of P2X(7) antagonists as novel therapeutic tools for the treatment of this type of pain...
  24. doi request reprint Antinociceptive effects of histamine H3 receptor antagonist in the preclinical models of pain in rats and the involvement of central noradrenergic systems
    Gin C Hsieh
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064, USA
    Brain Res 1354:74-84. 2010
    ..Our data also provide support that selective H(3) antagonists may represent a class of agents for the treatment of pain disorders...
  25. pmc Central and peripheral sites of action for CB₂ receptor mediated analgesic activity in chronic inflammatory and neuropathic pain models in rats
    Gin C Hsieh
    Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA
    Br J Pharmacol 162:428-40. 2011
    ..The present study was conducted to elucidate the CB₂ receptor expression in 'pain relevant' tissues and the potential sites of action of CB₂ agonism in rats...
  26. ncbi request reprint Discovery of potent furan piperazine sodium channel blockers for treatment of neuropathic pain
    Irene Drizin
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA
    Bioorg Med Chem 16:6379-86. 2008
    ....
  27. ncbi request reprint Assessing the role of metabotropic glutamate receptor 5 in multiple nociceptive modalities
    Chang Z Zhu
    Neuroscience Research, Global Pharmaceutical Research and Development, Dept 4N5, Bldg AP9A, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064 3500, USA
    Eur J Pharmacol 506:107-18. 2004
    ..These results suggest a role for mGlu5 receptors in multiple nociceptive modalities, though CNS side effects may be a limiting factor in developing mGlu5 receptor analgesic compounds...
  28. doi request reprint Comparison of mechanical allodynia and the affective component of inflammatory pain in rats
    Janel M Boyce-Rustay
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064 6115, USA
    Neuropharmacology 58:537-43. 2010
    ..These studies show that methods other than reflex based measures of pain such as affective pain models could be more predictive of efficacy/potency in the clinic...
  29. doi request reprint Discovery of TRPV1 antagonist ABT-116
    Brian S Brown
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Dept R4PM, AP10 207, 100 Abbott Park Road, Abbott Park, IL 60064 6100, USA
    Bioorg Med Chem Lett 20:3291-4. 2010
    ..Biological studies demonstrated potent in vitro and in vivo activity for 21, as well as suitable physicochemical and pharmacokinetic properties for advancement to clinical development for pain management...
  30. ncbi request reprint Electrophysiological and in vivo characterization of A-317567, a novel blocker of acid sensing ion channels
    G R Dube
    Abbott Laboratories, Neuroscience Research, Building AP9A Dept R4ND, Abbott Park, IL 60064 6118, USA
    Pain 117:88-96. 2005
    ..The discovery of A-317567 will greatly help to enhance our understanding of the physiological and pathophysiological role of ASICs...
  31. ncbi request reprint Morphine and ABT-594 (a nicotinic acetylcholine agonist) exert centrally mediated antinociception in the rat cyclophosphamide cystitis model of visceral pain
    S K Joshi
    Abbott Laboratories, Neuroscience Research, Abbott Park, Illinois 60064, USA
    J Pain 9:146-56. 2008
    ....
  32. ncbi request reprint Alpha-methylation at benzylic fragment of N-aryl-N'-benzyl ureas provides TRPV1 antagonists with better pharmacokinetic properties and higher efficacy in inflammatory pain model
    Arthur Gomtsyan
    Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064, USA
    Bioorg Med Chem Lett 17:3894-9. 2007
    ....
  33. doi request reprint α4β2 neuronal nicotinic receptor positive allosteric modulation: an approach for improving the therapeutic index of α4β2 nAChR agonists in pain
    Chih Hung Lee
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064 3500, USA
    Biochem Pharmacol 82:959-66. 2011
    ..Cardiovascular studies in anesthetized dogs achieve supra-therapeutic plasma concentrations of ABT-594 (>20-fold) without hemodynamic or electrophysiological effects using the co-administration paradigm...
  34. ncbi request reprint (R)-(5-tert-butyl-2,3-dihydro-1H-inden-1-yl)-3-(1H-indazol-4-yl)-urea (ABT-102) blocks polymodal activation of transient receptor potential vanilloid 1 receptors in vitro and heat-evoked firing of spinal dorsal horn neurons in vivo
    Carol S Surowy
    Abbott Laboratories, R4PM, AP9 1, 100 Abbott Park Road, Abbott Park, IL 60064 6118, USA
    J Pharmacol Exp Ther 326:879-88. 2008
    ..ABT-102 is a novel and selective TRPV1 antagonist with pharmacological and functional properties that support its advancement into clinical studies...
  35. ncbi request reprint A-425619 [1-isoquinolin-5-yl-3-(4-trifluoromethyl-benzyl)-urea], a novel and selective transient receptor potential type V1 receptor antagonist, blocks channel activation by vanilloids, heat, and acid
    Rachid El Kouhen
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064 6123, USA
    J Pharmacol Exp Ther 314:400-9. 2005
    ..These data show that A-425619 is a structurally novel, potent, and selective TRPV1 antagonist...
  36. ncbi request reprint Interleukin-1alphabeta gene-deficient mice show reduced nociceptive sensitivity in models of inflammatory and neuropathic pain but not post-operative pain
    Prisca Honore
    Abbott Laboratories, Dept R4N5, Bldg AP9A LL, 100 Abbott Park Road, Abbott Park, IL 60064, USA
    Behav Brain Res 167:355-64. 2006
    ....
  37. doi request reprint A-995662 [(R)-8-(4-methyl-5-(4-(trifluoromethyl)phenyl)oxazol-2-ylamino)-1,2,3,4-tetrahydronaphthalen-2-ol], a novel, selective TRPV1 receptor antagonist, reduces spinal release of glutamate and CGRP in a rat knee joint pain model
    Pamela S Puttfarcken
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, Illinois 60064, USA
    Pain 150:319-26. 2010
    ..These findings suggest that repeated dosing of TRPV1 antagonists enhances therapeutic potency and duration of action against OA pain, at least in part, by the sustained reduction in release of glutamate and CGRP from the spinal cord...
  38. ncbi request reprint (L)-Phenylglycine, but not necessarily other alpha2delta subunit voltage-gated calcium channel ligands, attenuates neuropathic pain in rats
    James J Lynch
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064, USA
    Pain 125:136-42. 2006
    ..These results suggest that additional mechanisms, besides alpha2delta interactions, may contribute to the effects of compounds like gabapentin, pregabalin and (L)-phenylglycine in neuropathic pain...
  39. doi request reprint Diaryldiamines with dual inhibition of the histamine H(3) receptor and the norepinephrine transporter and the efficacy of 4-(3-(methylamino)-1-phenylpropyl)-6-(2-(pyrrolidin-1-yl)ethoxy)naphthalen-1-ol in pain
    Robert J Altenbach
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, Illinois 60064 6100, United States
    J Med Chem 53:7869-73. 2010
    ..A series of compounds was designed as dual inhibitors of the H(3) receptor and the norepinephrine transporter. Compound 5 (rNET K(i) = 14 nM; rH(3)R K(i) = 37 nM) was found to be efficacious in a rat model of osteoarthritic pain...
  40. doi request reprint Chroman and tetrahydroquinoline ureas as potent TRPV1 antagonists
    Robert G Schmidt
    Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA
    Bioorg Med Chem Lett 21:1338-41. 2011
    ..The tetrahydroquinoline ureas were found to be potent CYP3A4 inhibitors, but replacement of bulky substituents at the nitrogen atom of the tetrahydroisoquinoline moiety with small groups such as methyl can minimize the inhibition...
  41. doi request reprint 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)...
  42. ncbi request reprint Structure-activity studies of a novel series of 5,6-fused heteroaromatic ureas as TRPV1 antagonists
    Irene Drizin
    Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064, USA
    Bioorg Med Chem 14:4740-9. 2006
    ..This derivative also showed selectivity versus other receptors in the CEREP screen and exhibited acceptable cardiovascular safety at levels exceeding the therapeutic dose...
  43. ncbi request reprint Structure-activity relationship studies on a series of novel, substituted 1-benzyl-5-phenyltetrazole P2X7 antagonists
    Derek W Nelson
    Abbott Laboratories, Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Park, Illinois 60064 6101, USA
    J Med Chem 49:3659-66. 2006
    ..Compound 15d was advanced to efficacy studies in a model of neuropathic pain where significant reversal of mechanical allodynia was observed at doses that did not affect motor coordination...
  44. doi request reprint Potentiation of analgesic efficacy but not side effects: co-administration of an α4β2 neuronal nicotinic acetylcholine receptor agonist and its positive allosteric modulator in experimental models of pain in rats
    Chang Z Zhu
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064 3500, USA
    Biochem Pharmacol 82:967-76. 2011
    ....
  45. doi request reprint Discovery and biological evaluation of potent, selective, orally bioavailable, pyrazine-based blockers of the Na(v)1.8 sodium channel with efficacy in a model of neuropathic pain
    Marc J C Scanio
    Global Pharmaceutical Research and Development, Abbott Laboratories, Dept R4PM, Bldg AP9A, 100 Abbott Park Road, Abbott Park, IL 60064 6117, United States
    Bioorg Med Chem 18:7816-25. 2010
    ..2. We further demonstrate that an example from this series is orally bioavailable and produces antinociceptive activity in vivo in a rodent model of neuropathic pain following oral administration...
  46. doi request reprint Characterization of a cannabinoid CB2 receptor-selective agonist, A-836339 [2,2,3,3-tetramethyl-cyclopropanecarboxylic acid [3-(2-methoxy-ethyl)-4,5-dimethyl-3H-thiazol-(2Z)-ylidene]-amide], using in vitro pharmacological assays, in vivo pain models, and
    Betty B Yao
    Neurological Diseases Research, Global Pharmaceutical Research and Development, Abbott Laboratories, R47W, AP9A, 100 Abbott Park Road, Abbott Park, IL 60064, USA
    J Pharmacol Exp Ther 328:141-51. 2009
    ..These data demonstrate that A-836339 is a useful tool for use of studying CB(2) receptor pharmacology and for investigation of the role of CB(2) receptor modulation for treatment of pain in preclinical animal models...
  47. doi request reprint Pharmacological modulation of movement-evoked pain in a rat model of osteoarthritis
    Prasant Chandran
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064 6115, USA
    Eur J Pharmacol 613:39-45. 2009
    ..As the model is clinically relevant, it will further enhance the mechanistic understanding of chronic arthritic joint pain and help in developing newer and better therapeutic strategies to manage osteoarthritis pain...
  48. doi request reprint Pharmacological modulation of brain activity in a preclinical model of osteoarthritis
    Jaymin Upadhyay
    Translational Sciences, Advanced Technology, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL, USA
    Neuroimage 64:341-55. 2013
    ....
  49. doi request reprint Subtype-selective Na(v)1.8 sodium channel blockers: identification of potent, orally active nicotinamide derivatives
    Michael E Kort
    Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064 6100, USA
    Bioorg Med Chem Lett 20:6812-5. 2010
    ..Representative compounds from this series displayed efficacy in rat models of inflammatory and neuropathic pain...
  50. doi request reprint Animal models of acute and chronic inflammatory and nociceptive pain
    Janel M Boyce-Rustay
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL, USA
    Methods Mol Biol 617:41-55. 2010
    ..This chapter will focus on rodent models of inflammatory and nociceptive pain that are most used in our laboratory for identification of novel antinociceptive compounds in drug discovery...
  51. pmc Coexpression and activation of TRPV1 suppress the activity of the KCNQ2/3 channel
    Xu Feng Zhang
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA
    J Gen Physiol 138:341-52. 2011
    ..Such neurons may thus have a lower threshold for activation, which may indirectly facilitate TRPV1 in integrating multiple noxious signals and/or in the establishment or maintenance of chronic pain...
  52. ncbi request reprint Correlation between brain/plasma ratios and efficacy in neuropathic pain models of selective metabotropic glutamate receptor 1 antagonists
    Guo Zhu Zheng
    Neuroscience Research, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064 6115, USA
    Bioorg Med Chem Lett 16:4936-40. 2006
    ..34, demonstrating only moderate efficacy in neuropathic pain models. On the other hand, antagonist 4b with a brain/plasma ratio of 2.70 was fully efficacious in neuropathic pain models...
  53. ncbi request reprint Rapid hit to lead evaluation of pyrazolo[3,4-d]pyrimidin-4-one as selective and orally bioavailable mGluR1 antagonists
    Xueqing Wang
    Neuroscience Research, Global Pharmaceutical Research and Development, AP9A L16, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL, USA
    Bioorg Med Chem Lett 17:4303-7. 2007
    ..These improvements were paralleled by rat PK study characterized by low clearance and quantitative bioavailability. Compound 2f represented a true lead-like molecule that is amenable for further lead optimization (LO) evaluation...
  54. ncbi request reprint ABT-594 (a nicotinic acetylcholine agonist): anti-allodynia in a rat chemotherapy-induced pain model
    James J Lynch
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Department R4N5, Bldg AP9A LL, 100 Abbott Park Road, Abbott Park, IL 60064 6115, USA
    Eur J Pharmacol 509:43-8. 2005
    ....
  55. pmc A-317491, a novel potent and selective non-nucleotide antagonist of P2X3 and P2X2/3 receptors, reduces chronic inflammatory and neuropathic pain in the rat
    Michael F Jarvis
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064 6123, USA
    Proc Natl Acad Sci U S A 99:17179-84. 2002
    ....
  56. ncbi request reprint Novel and potent 3-(2,3-dichlorophenyl)-4-(benzyl)-4H-1,2,4-triazole P2X7 antagonists
    William A Carroll
    Abbott Laboratories, Neuroscience Research, 100 Abbott Park Road, Abbott Park, IL 60064, USA
    Bioorg Med Chem Lett 17:4044-8. 2007
    ..Triazole-based P2X(7) antagonists were identified with similar potency to the lead compound 4 but with improved physiochemical properties. Compound 12 was active in a rat model of neuropathic pain...
  57. ncbi request reprint Dissociation between post-surgical pain behaviors and spinal Fos-like immunoreactivity in the rat
    Chang Z Zhu
    Neuroscience Research, Global Pharmaceutical Research, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064 3500, USA
    Eur J Pharmacol 531:108-17. 2006
    ....
  58. ncbi request reprint Painful purinergic receptors
    Diana Donnelly-Roberts
    Abbott Laboratories, R4PM, AP9A 311, 100 Abbott Park Road, Abbott Park, IL 60064, USA
    J Pharmacol Exp Ther 324:409-15. 2008
    ..This perspective highlights some of the recent advances to identify selective P2 receptor ligands, which has enhanced the investigation of ATP-related modulation of pain sensitivity...
  59. ncbi request reprint Alteration of dorsal root ganglion P2X3 receptor expression and function following spinal nerve ligation in the rat
    Karen Kage
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064 6123, USA
    Exp Brain Res 147:511-9. 2002
    ..These remaining receptors may provide a P2X(3) receptor-mediated component to neuropathic pain...
  60. doi request reprint Characterization of Fasudil in preclinical models of pain
    Janel M Boyce-Rustay
    Abbott Laboratories, Abbott Park, Illinois 60064, USA
    J Pain 11:941-9. 2010
    ..These results suggest that the acute administration of a ROCK inhibitor produces efficacy in both neuropathic and nociceptive pain states at doses devoid of locomotor side effects, with specific effects on WDR neurons...
  61. ncbi request reprint Differential action potentials and firing patterns in injured and uninjured small dorsal root ganglion neurons after nerve injury
    Xu Feng Zhang
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA
    Brain Res 1009:147-58. 2004
    ....
  62. doi request reprint KCNQ2/3 openers show differential selectivity and site of action across multiple KCNQ channels
    Di Zhang
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064 6118, USA
    J Neurosci Methods 200:54-62. 2011
    ..The high-throughput thallium influx assays should prove useful for rapid characterization of KCNQ openers and in guiding efforts to identify selective compounds for advancement towards the clinic...
  63. ncbi request reprint Attenuation of mechanical allodynia by clinically utilized drugs in a rat chemotherapy-induced neuropathic pain model
    James J Lynch
    Neuroscience Research, Global Pharmaceutical Research and Development, Dept R4N5, Abbott Laboratories, Bldg AP9A LL, 100 Abbott Park Road, Abbott Park, IL 60064 6115, USA
    Pain 110:56-63. 2004
    ..The surprisingly good effects observed with acetaminophen warrant further investigation of its mechanism(s) of action in neuropathic pain...
  64. ncbi request reprint Structure-activity relationships of alpha-amino acid ligands for the alpha2delta subunit of voltage-gated calcium channels
    Kathleen H Mortell
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064, USA
    Bioorg Med Chem Lett 16:1138-41. 2006
    ..Potent analogs were identified. Their activity in an in vivo pain assay is described...
  65. ncbi request reprint Role of central and peripheral mGluR5 receptors in post-operative pain in rats
    Chang Z Zhu
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064 3500, USA
    Pain 114:195-202. 2005
    ..In addition, the data suggest that mGluR5 antagonists could offer a new therapeutic approach to the treatment of post-operative pain...
  66. doi request reprint 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
    ....
  67. ncbi request reprint Novel transient receptor potential vanilloid 1 receptor antagonists for the treatment of pain: structure-activity relationships for ureas with quinoline, isoquinoline, quinazoline, phthalazine, quinoxaline, and cinnoline moieties
    Arthur Gomtsyan
    Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, Illinois 60064, USA
    J Med Chem 48:744-52. 2005
    ....
  68. ncbi request reprint Comparison of the ability of adenosine kinase inhibitors and adenosine receptor agonists to attenuate thermal hyperalgesia and reduce motor performance in rats
    Michael F Jarvis
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, R04PM, AP9A 2, 100 Abbott Park Road, IL 60064 6123, USA
    Pharmacol Biochem Behav 73:573-81. 2002
    ....
  69. ncbi request reprint Efficacy of systemic morphine suggests a fundamental difference in the mechanisms that generate bone cancer vs inflammatory pain
    Nancy M Luger
    Department of Preventive Sciences, Schools of Dentistry and Medicine, University of Minnesota, Minneapolis, MN 55455, USA
    Pain 99:397-406. 2002
    ..inflammatory pain. These results indicate that this model may be useful in defining drug therapies that are targeted for complex bone cancer pain syndromes...
  70. ncbi request reprint Tooth extraction-induced internalization of the substance P receptor in trigeminal nucleus and spinal cord neurons: imaging the neurochemistry of dental pain
    Mary Ann C Sabino
    Department of Preventive Sciences, University of Minnesota, 18 208 Moos Tower, 515 Delaware Street SE, Minneapolis, MN 55455, USA
    Pain 95:175-86. 2002
    ..Defining the population of neurons activated in orofacial pain and whether analgesics modify the activation of these neurons should provide insight into the mechanisms that generate and maintain acute and chronic orofacial pain...