J D Brioni

Summary

Affiliation: Abbott Laboratories
Country: USA

Publications

  1. ncbi request reprint Fatty acid amide hydrolase inhibitors display broad selectivity and inhibit multiple carboxylesterases as off-targets
    Di Zhang
    Neuroscience Research, Advanced Technology and Process Research and Development, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA
    Neuropharmacology 52:1095-105. 2007
  2. ncbi request reprint 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
  3. pmc Activation of dopamine D4 receptors by ABT-724 induces penile erection in rats
    Jorge D Brioni
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA
    Proc Natl Acad Sci U S A 101:6758-63. 2004
  4. doi request reprint Discovery of histamine H3 antagonists for the treatment of cognitive disorders and Alzheimer's disease
    Jorge D Brioni
    Neuroscience Research Dept 4MN, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064, USA
    J Pharmacol Exp Ther 336:38-46. 2011
  5. ncbi request reprint Characterization of the ATP-sensitive potassium channels (KATP) expressed in guinea pig bladder smooth muscle cells
    M Gopalakrishnan
    Neurological and Urological Diseases Research, Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, Illinois, USA
    J Pharmacol Exp Ther 289:551-8. 1999
  6. pmc Pharmacology of human sulphonylurea receptor SUR1 and inward rectifier K(+) channel Kir6.2 combination expressed in HEK-293 cells
    M Gopalakrishnan
    Neurological and Urological Diseases Research, Abbott Laboratories, Abbott Park, Illinois, IL 60064, USA
    Br J Pharmacol 129:1323-32. 2000
  7. ncbi request reprint Pharmacological and molecular analysis of ATP-sensitive K(+) channels in the pig and human detrusor
    S A Buckner
    Neurological and Urological Diseases Research, Pharmaceutical Products Division, Abbott Laboratories, D47C, Bldg AP9, First Floor, 100 Abbott Park Road, Abbott Park, IL 60064 6118, USA
    Eur J Pharmacol 400:287-95. 2000
  8. ncbi request reprint Functional implication of spare ATP-sensitive K(+) channels in bladder smooth muscle cells
    C C Shieh
    Neurological and Urological Diseases Research, Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, Illinois 60064-6125, USA
    J Pharmacol Exp Ther 296:669-75. 2001
  9. ncbi request reprint Dual mechanism of action of nicorandil on rabbit corpus cavernosal smooth muscle tone
    G C Hsieh
    Neurological and Urological Diseases Research, Abbott Laboratories, Abbott Park, Illinois 60064 6119, USA
    Int J Impot Res 13:240-6. 2001
  10. ncbi request reprint ABT-866, a novel alpha(1A)-adrenoceptor agonist with antagonist properties at the alpha(1B)- and alpha(1D)-adrenoceptor subtypes
    Steven A Buckner
    Neuroscience Research, Global Pharmaceutical Research and Development, Department R4ND, Bldg AP9A, Third Floor, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064 6125, USA
    Eur J Pharmacol 449:159-65. 2002

Detail Information

Publications76

  1. ncbi request reprint Fatty acid amide hydrolase inhibitors display broad selectivity and inhibit multiple carboxylesterases as off-targets
    Di Zhang
    Neuroscience Research, Advanced Technology and Process Research and Development, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA
    Neuropharmacology 52:1095-105. 2007
    ....
  2. ncbi request reprint 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...
  3. pmc Activation of dopamine D4 receptors by ABT-724 induces penile erection in rats
    Jorge D Brioni
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA
    Proc Natl Acad Sci U S A 101:6758-63. 2004
    ..The ability of ABT-724 to facilitate penile erection together with the favorable side-effect profile indicates that ABT-724 could be useful for the treatment of erectile dysfunction...
  4. doi request reprint Discovery of histamine H3 antagonists for the treatment of cognitive disorders and Alzheimer's disease
    Jorge D Brioni
    Neuroscience Research Dept 4MN, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064, USA
    J Pharmacol Exp Ther 336:38-46. 2011
    ..Ongoing clinical studies will be able to determine the utility of H(3) antagonists for the treatment of cognitive disorders in humans...
  5. ncbi request reprint Characterization of the ATP-sensitive potassium channels (KATP) expressed in guinea pig bladder smooth muscle cells
    M Gopalakrishnan
    Neurological and Urological Diseases Research, Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, Illinois, USA
    J Pharmacol Exp Ther 289:551-8. 1999
    ....
  6. pmc Pharmacology of human sulphonylurea receptor SUR1 and inward rectifier K(+) channel Kir6.2 combination expressed in HEK-293 cells
    M Gopalakrishnan
    Neurological and Urological Diseases Research, Abbott Laboratories, Abbott Park, Illinois, IL 60064, USA
    Br J Pharmacol 129:1323-32. 2000
    ..2 channels co-expressed in HEK-293 cells resemble those typical of native K(ATP) channels described in pancreatic and neuronal tissues...
  7. ncbi request reprint Pharmacological and molecular analysis of ATP-sensitive K(+) channels in the pig and human detrusor
    S A Buckner
    Neurological and Urological Diseases Research, Pharmaceutical Products Division, Abbott Laboratories, D47C, Bldg AP9, First Floor, 100 Abbott Park Road, Abbott Park, IL 60064 6118, USA
    Eur J Pharmacol 400:287-95. 2000
    ....
  8. ncbi request reprint Functional implication of spare ATP-sensitive K(+) channels in bladder smooth muscle cells
    C C Shieh
    Neurological and Urological Diseases Research, Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, Illinois 60064-6125, USA
    J Pharmacol Exp Ther 296:669-75. 2001
    ..These findings demonstrate that the reduction in membrane excitability by KCOs is associated with membrane hyperpolarization, and that a low amount of K(ATP) channel opening is sufficient to suppress bladder smooth muscle contraction...
  9. ncbi request reprint Dual mechanism of action of nicorandil on rabbit corpus cavernosal smooth muscle tone
    G C Hsieh
    Neurological and Urological Diseases Research, Abbott Laboratories, Abbott Park, Illinois 60064 6119, USA
    Int J Impot Res 13:240-6. 2001
    ..The results of the present study indicate that nicorandil can relax rabbit cavernosal tissue in vitro via a mechanism that involves activation of K(ATP) channels and stimulation of soluble guanylate cyclase...
  10. ncbi request reprint ABT-866, a novel alpha(1A)-adrenoceptor agonist with antagonist properties at the alpha(1B)- and alpha(1D)-adrenoceptor subtypes
    Steven A Buckner
    Neuroscience Research, Global Pharmaceutical Research and Development, Department R4ND, Bldg AP9A, Third Floor, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064 6125, USA
    Eur J Pharmacol 449:159-65. 2002
    ....
  11. ncbi request reprint A-315456: a selective alpha(1D)-adrenoceptor antagonist with minimal dopamine D(2) and 5-HT(1A) receptor affinity
    S A Buckner
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064 6118, USA
    Eur J Pharmacol 433:123-7. 2001
    ..These studies indicate that A-315456 is a potent and selective alpha(1D)-antagonist that may serve as a useful pharmacological ligand to probe the physiological role of the alpha(1D)-adrenoceptor subtype in normal and disease states...
  12. 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...
  13. ncbi request reprint Activation of soluble guanylate cyclase causes relaxation of corpus cavernosum tissue: synergism of nitric oxide and YC-1
    M Nakane
    Neuroscience, Global Pharmaceutical Research, Abbott Laboratories, Abbott Park, Illinois 60064 6119, USA
    Int J Impot Res 14:121-7. 2002
    ....
  14. ncbi request reprint [3H] A-369508 ([2-[4-(2-cyanophenyl)-1-piperazinyl]-N-(3-methylphenyl) acetamide): an agonist radioligand selective for the dopamine D4 receptor
    Robert B Moreland
    Neuroscience Research Global Pharmaceutical Research and Development, AP9 Room 1125, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064 6118, USA
    Eur J Pharmacol 497:147-54. 2004
    ....
  15. ncbi request reprint Functional characterization of the novel neuronal nicotinic acetylcholine receptor ligand GTS-21 in vitro and in vivo
    C A Briggs
    Abbott Laboratories, Abbott Park, Illinois 60064, USA
    Pharmacol Biochem Behav 57:231-41. 1997
    ..Neither was it active in the elevated plus maze anxiety model (0.19-6.2 micromol/kg.IP) in normal mice. However, GTS-21 did improve learning performance of monkeys in the delayed matching-to-sample task (32-130 nmol/kg.i.m.)...
  16. pmc Characterization of a novel ATP-sensitive K+ channel opener, A-251179, on urinary bladder relaxation and cystometric parameters
    C C Shieh
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA
    Br J Pharmacol 151:467-75. 2007
    ..This study reports the characterization of 4-methyl-N-(2,2,2-trichloro-1-(3-pyridin-3-ylthioureido)ethyl)benzamide (A-251179) as a K(ATP) channel opener...
  17. ncbi request reprint Pharmacological properties of A-204176, a novel and selective alpha1A adrenergic agonist, in in vitro and in vivo models of urethral function
    A B O'Neill
    Neurological and Urological Diseases Research, Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, IL 60064, USA
    Life Sci 70:181-97. 2001
    ..These data indicate that A-204176 may represent a useful pharmacological tool to investigate the functional role of the alpha1A adrenoceptor in the urethra and to elucidate the lack of uroselectivity observed in vivo...
  18. ncbi request reprint Histaminergic ligands attenuate barrel rotation in rats following unilateral labyrinthectomy
    J B Pan
    Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, IL, USA
    Methods Find Exp Clin Pharmacol 20:771-7. 1998
    ..These results indicate that this model may be a potential tool for testing novel drugs for antivertigo effects and provide better support to the role of the histaminergic system in the control of vestibular function...
  19. 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
    ....
  20. 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...
  21. ncbi request reprint Structure-activity relationship of triazafluorenone derivatives as potent and selective mGluR1 antagonists
    Guo Zhu Zheng
    Neuroscience Research, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, Illinois 60064 6115, USA
    J Med Chem 48:7374-88. 2005
    ..Compound 1n, for example, was a very potent mGluR1 antagonist (IC50 = 3 nM) and demonstrated full efficacy in various in vivo animal pain models...
  22. ncbi request reprint 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...
  23. ncbi request reprint Association of Catsper1 or -2 with Ca(v)3.3 leads to suppression of T-type calcium channel activity
    Di Zhang
    Neuroscience Research and Advanced Technology, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, Illinois 60064, USA
    J Biol Chem 281:22332-41. 2006
    ..These studies demonstrate that CatSper1 and CatSper2 can associate with and modulate the function of the Ca(v)3.3 channel, which might be important in the regulation of sperm function...
  24. ncbi request reprint Discovery of 3-methyl-N-(1-oxy-3',4',5',6'-tetrahydro-2'H-[2,4'-bipyridine]-1'-ylmethyl)benzamide (ABT-670), an orally bioavailable dopamine D4 agonist for the treatment of erectile dysfunction
    Meena V Patel
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, Illinois 60064 3500, USA
    J Med Chem 49:7450-65. 2006
    ..The N-oxy-2-pyridinyl moiety not only provided the structural motif required for agonist function but also reduced metabolism rates. The SAR study leading to the discovery of 6b is described herein...
  25. ncbi request reprint Dopamine D4 receptor signaling in the rat paraventricular hypothalamic nucleus: Evidence of natural coupling involving immediate early gene induction and mitogen activated protein kinase phosphorylation
    Robert S Bitner
    Abbott Laboratories, Neuroscience Research, Abbott Park, IL 60064 3500, USA
    Neuropharmacology 50:521-31. 2006
    ..These findings provide additional evidence that the PVN may be a site of dopamine D4 receptor-mediated proerectile activity...
  26. ncbi request reprint A-412997, a selective dopamine D4 agonist, improves cognitive performance in rats
    Kaitlin E Browman
    Neuroscience Research, Abbott Laboratories, AP9A, R4N5, 100 Abbott Park Road, Abbott Park, IL 60064 6115, USA
    Pharmacol Biochem Behav 82:148-55. 2005
    ..CP226269 showed a significant enhancement in the 5-trial inhibitory avoidance model. These results support a role for the dopamine D4 receptor subtype in cognition...
  27. ncbi request reprint 1-aryl-3-(4-pyridine-2-ylpiperazin-1-yl)propan-1-one oximes as potent dopamine D4 receptor agonists for the treatment of erectile dysfunction
    Teodozyj Kolasa
    Neuroscience Research, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, Illinois 60064 6101, USA
    J Med Chem 49:5093-109. 2006
    ..Our results suggest that the oximes provide a novel structural linker for 4-arylpiperazine-based D4 agonists, possessing leadlike quality and with potential to develop a new class of potent and selective dopamine D4 receptor agonists...
  28. 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...
  29. ncbi request reprint Acrylamide analog as a novel nitric oxide-independent soluble guanylyl cyclase activator
    Masaki Nakane
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, USA
    J Pharmacol Sci 102:231-8. 2006
    ..This novel activator of sGC may have potential efficacy for the treatment of a variety of disorders associated with reduced NO signaling...
  30. doi request reprint In-vivo histamine H3 receptor antagonism activates cellular signaling suggestive of symptomatic and disease modifying efficacy in Alzheimer's disease
    R Scott Bitner
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064, USA
    Neuropharmacology 60:460-6. 2011
    ....
  31. 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...
  32. doi request reprint 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...
  33. doi request reprint 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...
  34. 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...
  35. doi request reprint 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)...
  36. doi request reprint Synthesis and evaluation of benzothiazole-based analogues as novel, potent, and selective fatty acid amide hydrolase inhibitors
    Xueqing Wang
    Neuroscience Research, Global Pharmaceutical Research and Development, AP10 303, Abbott Laboratories, Abbott Park, Illinois 60064, USA
    J Med Chem 52:170-80. 2009
    ..These compounds may provide useful tools for the study of FAAH and the endocannabinoid system...
  37. doi request reprint Localization of histamine H4 receptors in the central nervous system of human and rat
    Marina I Strakhova
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Department R4MN, Abbott Park, Illinois 60064, USA
    Brain Res 1250:41-8. 2009
    ..Our observations provide evidence of the H(4) presence in both human and rodent CNS and offer some insight into possible role of H(4) in itch and pain...
  38. 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...
  39. doi request reprint 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
    ....
  40. 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)...
  41. 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
    ....
  42. doi request reprint 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...
  43. 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...
  44. ncbi request reprint A-412997 is a selective dopamine D4 receptor agonist in rats
    Robert B Moreland
    Neuroscience Research, Global Pharmaceutical Research and Development, AP9A Room 219, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, Illinois, 60064 6123, USA
    Pharmacol Biochem Behav 82:140-7. 2005
    ..A-412997 is a highly selective dopamine D4 receptor agonist and a useful tool to understand the role of dopamine D4 receptors in rat models of central nervous system processes and disease...
  45. ncbi request reprint Dopamine D4 ligands and models of receptor activation: 2-(4-pyridin-2-ylpiperazin-1-ylmethyl)-1H-benzimidazole and related heteroarylmethylarylpiperazines exhibit a substituent effect responsible for additional efficacy tuning
    Andrew O Stewart
    Department R4ND, Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, Illinois 60064 6115, USA
    J Med Chem 47:2348-55. 2004
    ..The structural similarity between partial agonist and antagonist, within this subset of ligands, and lack of bioisosterism for this substituent effect are key phenomena for these hypotheses...
  46. ncbi request reprint Emerging pharmacologic approaches for the treatment of lower urinary tract disorders
    Robert B Moreland
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064 6118, USA
    J Pharmacol Exp Ther 308:797-804. 2004
    ..New peripheral targets as well as centrally acting agents represent potential emerging therapies. In this review, the pharmacologic basis of treatment of these disorders is discussed with special emphasis on emerging new therapeutics...
  47. ncbi request reprint Central mechanisms regulating penile erection in conscious rats: the dopaminergic systems related to the proerectile effect of apomorphine
    Gin C Hsieh
    Neuroscience Research, Abbott Laboratories, Abbott Park, Illinois 60064 6119, USA
    J Pharmacol Exp Ther 308:330-8. 2004
    ..These results suggest that the proerectile action of apomorphine in rats is mediated at supraspinal levels and that this effect is not mimicked by a D2 receptor agonist but associated with activation of D4 receptors...
  48. ncbi request reprint A cell-based microarrayed compound screening format for identifying agonists of G-protein-coupled receptors
    Sujatha M Gopalakrishnan
    Advanced Technology, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA
    Anal Biochem 321:192-201. 2003
    ..Excellent confirmation rates coupled with enhanced efficiency and throughput enable microARCS to serve as an alternative platform for the screening and identification of novel GPCR agonists...
  49. ncbi request reprint K-ATP opener-mediated attenuation of spontaneous bladder contractions in ligature-intact, partial bladder outlet obstructed rats
    James J Lynch
    Neuroscience Research, Global Pharmaceutical Research and Development, Department R4N5, Bldg AP9A LL, Abbott Laboratories, 100 Abbott Park Road, IL 60064 6115, USA
    Life Sci 72:1931-41. 2003
    ....
  50. ncbi request reprint Effects of ATP-sensitive K+ channel openers and tolterodine on involuntary bladder contractions in a pig model of partial bladder outlet obstruction
    Thomas A Fey
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, Illinois 60064 6118, USA
    Neurourol Urodyn 22:147-55. 2003
    ..To compare in vivo the efficacy, potency, and bladder-vascular selectivity of ATP-sensitive potassium channel openers (KCOs), YM934 and (-)-cromakalim to a muscarinic antagonist, tolterodine in a novel partial outlet obstructed pig model...
  51. ncbi request reprint YC-1 potentiates the nitric oxide/cyclic GMP pathway in corpus cavernosum and facilitates penile erection in rats
    Gin C Hsieh
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064 6119, USA
    Eur J Pharmacol 458:183-9. 2003
    ..These biochemical events may be related to the pro-erectile properties of YC-1 in vivo...
  52. ncbi request reprint A-350619: a novel activator of soluble guanylyl cyclase
    Loan N Miller
    Neuroscience Research, Global Pharmaceutical Research and Development, AP9, Room 1125, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064 6119, USA
    Life Sci 72:1015-25. 2003
    ..Activation of soluble guanylyl cyclase in cavernosum tissue as an alternate method of enhancing the effect of NO may provide a novel treatment of sexual dysfunction...
  53. ncbi request reprint N-[3-(1H-imidazol-4-ylmethyl)phenyl]ethanesulfonamide (ABT-866, 1),(1) a novel alpha(1)-adrenoceptor ligand with an enhanced in vitro and in vivo profile relative to phenylpropanolamine and midodrine
    Robert J Altenbach
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, Illinois 60064, USA
    J Med Chem 45:4395-7. 2002
    ..4) and alpha(1D) (rat aorta, pA(2) = 6.2) antagonism. An in vivo dog model showed 1 to be more selective for the urethra over the vasculature than A-61603 (2), ST-1059 (3, the active metabolite of midodrine), and phenylpropanolamine (4)...
  54. ncbi request reprint (-)-(9S)-9-(3-Bromo-4-fluorophenyl)-2,3,5,6,7,9-hexahydrothieno[3,2-b]quinolin-8(4H)-one 1,1-dioxide (A-278637): a novel ATP-sensitive potassium channel opener efficacious in suppressing urinary bladder contractions. II. in vivo characterization
    Michael E Brune
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Illinois 60064, USA
    J Pharmacol Exp Ther 303:387-94. 2002
    ....
  55. ncbi request reprint (-)-(9S)-9-(3-Bromo-4-fluorophenyl)-2,3,5,6,7,9-hexahydrothieno[3,2-b]quinolin-8(4H)-one 1,1-dioxide (A-278637): a novel ATP-sensitive potassium channel opener efficacious in suppressing urinary bladder contractions. I. In vitro characterization
    Murali Gopalakrishnan
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Illinois 60064, USA
    J Pharmacol Exp Ther 303:379-86. 2002
    ..The pharmacological profile of A-278637 represents an attractive basis for further investigations of selective K(ATP) channel openers for the treatment of overactive bladder via myogenic etiology...
  56. ncbi request reprint Synthesis and structure-activity relationships of a novel series of 2,3,5,6,7,9-hexahydrothieno[3,2-b]quinolin-8(4H)-one 1,1-dioxide K(ATP) channel openers: discovery of (-)-(9S)-9-(3-bromo-4-fluorophenyl)-2,3,5,6,7,9- hexahydrothieno[3,2-b]quinolin-8(4H)
    William A Carroll
    Abbott Laboratories, Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Park, IL 60064 6101, USA
    J Med Chem 47:3163-79. 2004
    ..Compound 14 showed approximately 5-fold greater selectivity than 1 in vivo and supports the concept that bladder-selective K(ATP) channel openers may have utility in the treatment of overactive bladder...
  57. ncbi request reprint 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...
  58. ncbi request reprint Synthesis and evaluation of 3-aryl piperidine analogs as potent and efficacious dopamine D4 receptor agonists
    Xueqing Wang
    Neuroscience Research, Global Pharmaceutical Research and Development, AP9A L16, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064, USA
    Bioorg Med Chem 13:4667-78. 2005
    ..The synthesis and structure-activity relationship (SAR) studies that led to the identification of these compounds are discussed...
  59. ncbi request reprint Antidepressant-like effect of D(2/3) receptor-, but not D(4) receptor-activation in the rat forced swim test
    Ana M Basso
    Abbott Laboratories, Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Park, IL 60064, USA
    Neuropsychopharmacology 30:1257-68. 2005
    ..The pharmacological selectivity of the compounds tested suggests that the antidepressant-like effects of quinpirole are most likely mediated mainly by D(2) and to a lesser extent by D(3) but not D(4) receptors...
  60. ncbi request reprint 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...
  61. 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...
  62. ncbi request reprint Effects of selective dopamine receptor subtype agonists on cardiac contractility and regional haemodynamics in rats
    James S Polakowski
    Pharmaceutical Discovery, Global Pharmaceutical R and D, Abbott Laboratories, Abbott Park, Illinois 60064 6119, USA
    Clin Exp Pharmacol Physiol 31:837-41. 2004
    ..Hence, by comparison, agonism of the D4 receptor has little effect in the cardiovascular system of the rat relative to the other dopamine receptor subtype agonists tested...
  63. ncbi request reprint Synthesis and activity of 2-[4-(4-[3H]-2-cyanophenyl)piperazinyl]-N-(2,4,6-[3H]3-3-methylphenyl)acetamide: a selective dopamine D4 receptor agonist and radioligand
    Mark A Matulenko
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, AP9A L16, 100 Abbott Park Road, Abbott Park, IL 60064 6115, USA
    Bioorg Med Chem Lett 14:5095-8. 2004
    ..The synthesis, biological, and radioactivity of this new agonist radioligand as well as preliminary SAR will be discussed...
  64. ncbi request reprint Comparative pharmacology of human dopamine D(2)-like receptor stable cell lines coupled to calcium flux through Galpha(qo5)
    Robert B Moreland
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA
    Biochem Pharmacol 68:761-72. 2004
    ....
  65. ncbi request reprint Discovery of 2-(4-pyridin-2-ylpiperazin-1-ylmethyl)-1H-benzimidazole (ABT-724), a dopaminergic agent with a novel mode of action for the potential treatment of erectile dysfunction
    Marlon Cowart
    Department of Neuroscience Research, Abbott Laboratories, Abbott Park, IL 60064 6123, USA
    J Med Chem 47:3853-64. 2004
    ..Distinctive structural features were discovered that are associated with D4 selective agonism in this series of analogues...
  66. ncbi request reprint Synthesis and functional activity of (2-aryl-1-piperazinyl)-N-(3-methylphenyl)acetamides: selective dopamine D4 receptor agonists
    Mark A Matulenko
    Neuroscience Research, Global Pharmaceutical Research, Abbott Laboratories, Abbott Park, IL 60064, USA
    Bioorg Med Chem 12:3471-83. 2004
    ..Systematic evaluation of the substitution on the aryl piperazine portion revealed a significant effect on functional activity. The synthesis and biological activity of these new dopamine D(4) agonists is discussed...
  67. ncbi request reprint Dopamine D2, but not D4, receptor agonists are emetogenic in ferrets
    Mark A Osinski
    Integrative Pharmacology, Global Pharmaceutical Research and Discovery, Abbott Laboratories, R46R AP9 1, 100 Abbott Park Road, Abbott Park, IL 60064 6119, USA
    Pharmacol Biochem Behav 81:211-9. 2005
    ..Thus, dopamine D2 and/or D3 receptor agonists elicit emesis, while dopamine D1/D5 or D4 receptor-selective agonists are devoid of emetic properties...
  68. ncbi request reprint Comparison of alpha 1-adrenoceptor agonists in canine urethral pressure profilometry and abdominal leak point pressure models
    M E Brune
    Neurological and Urological Disease Research, Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, Illinois 60064-6118, USA
    J Urol 166:1555-9. 2001
    ..This leak point pressure test appears be useful for the preclinical evaluation of compounds used to treat stress urinary incontinence...
  69. pmc In vitro and in vivo characterization of A-940894: a potent histamine H4 receptor antagonist with anti-inflammatory properties
    M I Strakhova
    Neuroscience Research, Global Pharmaceutical Research Division, Abbott Laboratories, Abbott Park, IL 60064, USA
    Br J Pharmacol 157:44-54. 2009
    ..In this report, we describe the in vitro and in vivo anti-inflammatory properties of a potent histamine H4 receptor antagonist, A-940894 (4-piperazin-1-yl-6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-d]pyrimidin-2-ylamine)...
  70. pmc The histamine H3 receptor: an attractive target for the treatment of cognitive disorders
    T A Esbenshade
    Division of Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA
    Br J Pharmacol 154:1166-81. 2008
    ..The discovery of effective H3 antagonists as therapeutic agents for the novel treatment of cognitive disorders will only be accomplished through continued research efforts that further our insights into the functions of the H3 receptor...
  71. pmc Blockade of mGluR1 receptor results in analgesia and disruption of motor and cognitive performances: effects of A-841720, a novel non-competitive mGluR1 receptor antagonist
    O El-Kouhen
    Neuroscience Research, Global Pharmaceutical Research Division, Abbott Laboratories, Abbott Park, IL 60064, USA
    Br J Pharmacol 149:761-74. 2006
    ..To further assess the clinical potential of the blockade of metabotropic glutamate receptors (mGluR1) for the treatment of pain...
  72. ncbi request reprint Molecular characterization of human SUR2-containing K(ATP) channels
    R Davis-Taber
    Neurological and Urological Diseases Research, Dept 47C, APgA, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064, USA
    Gene 256:261-70. 2000
    ..Collectively, our findings demonstrate that various SUR2 splice variants have distinct expression patterns and can form functional K(ATP) channels...
  73. ncbi request reprint In vivo evaluation of the potency and bladder-vascular selectivity of the ATP-sensitive potassium channel openers (-)-cromakalim, ZD6169 and WAY-133537 in rats
    A C Fabiyi
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL, USA
    BJU Int 91:284-90. 2003
    ..To compare in vivo the potency and bladder-vascular selectivity of ATP-sensitive potassium channel openers (KCOs) (-)-cromakalim, WAY-133537 and ZD6169 and a muscarinic antagonist, tolterodine in rats...
  74. pmc Enhancement of apomorphine-induced penile erection in the rat by a selective alpha(1D)-adrenoceptor antagonist
    Hiroya Mizusawa
    Department of Clinical Pharmacology, University of Lund, Sweden
    Br J Pharmacol 136:701-8. 2002
    ..5. The present findings show that there is a functional predominance of the alpha(1D)-AR subtype in the rat erectile tissue, and that blockade of this receptor facilitates rat penile erection induced by a suboptimal dose of apomorphine...
  75. pmc The novel calpain inhibitor A-705253 potently inhibits oligomeric beta-amyloid-induced dynamin 1 and tau cleavage in hippocampal neurons
    Roxana C Sinjoanu
    Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
    Neurochem Int 53:79-88. 2008
    ..Collectively, these results suggest that, indeed, specific calpain inhibitors could play an important role in the treatment of Alzheimer's disease...
  76. ncbi request reprint Meeting report for the ASPET Ray Fuller Symposium: lower urinary tract disorders: physiology, pharmacology, and therapeutic approaches
    Martin C Michel
    Department of Medicine, University of Essen, Germany
    J Pharmacol Exp Ther 303:431-7. 2002