William R Kem

Summary

Affiliation: University of Florida
Country: USA

Publications

  1. ncbi request reprint Alzheimer's drug design based upon an invertebrate toxin (anabaseine) which is a potent nicotinic receptor agonist
    W R Kem
    Department of Pharmacology and Therapeutics, University of Florida College of Medicine, Gainesville 32610 0267, USA
    Invert Neurosci 3:251-9. 1997
  2. ncbi request reprint The brain alpha7 nicotinic receptor may be an important therapeutic target for the treatment of Alzheimer's disease: studies with DMXBA (GTS-21)
    W R Kem
    Department of Pharmacology and Experimental Therapeutics, University of Florida College of Medicine, Gainesville 32610 0267, USA
    Behav Brain Res 113:169-81. 2000
  3. ncbi request reprint Inhibition of barnacle larval settlement and crustacean toxicity of some hoplonemertine pyridyl alkaloids
    William R Kem
    Department of Pharmacology and Therapeutics, University of Florida College of Medicine, Gainesville, FL 32610 0267, USA
    Biomol Eng 20:355-61. 2003
  4. ncbi request reprint Hydroxy metabolites of the Alzheimer's drug candidate 3-[(2,4-dimethoxy)benzylidene]-anabaseine dihydrochloride (GTS-21): their molecular properties, interactions with brain nicotinic receptors, and brain penetration
    William R Kem
    Department of Pharmacology and Therapeutics, College of Medicine, University of Florida, Gainesville, FL 32610 0267, USA
    Mol Pharmacol 65:56-67. 2004
  5. ncbi request reprint Nicotinic receptor inhibition by Tetraponera ant alkaloids
    William R Kem
    Department of Pharmacology and Therapeutics, University of Florida College of Medicine, Gainesville, Florida 32610 0267, USA
    Cell Mol Neurobiol 24:535-51. 2004
  6. pmc Activation and desensitization of nicotinic alpha7-type acetylcholine receptors by benzylidene anabaseines and nicotine
    Roger L Papke
    Department of Pharmacology and Therapeutics, University of Florida College of Medicine, Gainesville, FL 32610 0267, USA
    J Pharmacol Exp Ther 329:791-807. 2009
  7. pmc Positive modulation of alpha7 nAChR responses in rat hippocampal interneurons to full agonists and the alpha7-selective partial agonists, 4OH-GTS-21 and S 24795
    Gretchen Y López-Hernández
    Department of Pharmacology and Therapeutics, University of Florida, College of Medicine, Gainesville, FL 32610 0267, USA
    Neuropharmacology 56:821-30. 2009
  8. pmc Point-to-point ligand-receptor interactions across the subunit interface modulate the induction and stabilization of conformational states of alpha7 nAChR by benzylidene anabaseines
    Matthew D Isaacson
    Department of Pharmacology and Therapeutics, University of Florida College of Medicine, P O Box 100267, Gainesville, FL 32610, United States
    Biochem Pharmacol 85:817-28. 2013
  9. ncbi request reprint The structural basis for GTS-21 selectivity between human and rat nicotinic alpha7 receptors
    Clare Stokes
    Department of Pharmacology and Therapeutics, P O Box 100267, 1600 SW Archer Rd, University of Florida, College of Medicine, Gainesville, FL 32610, USA
    Mol Pharmacol 66:14-24. 2004
  10. doi request reprint A computational study of the binding of 3-(arylidene) anabaseines to two major brain nicotinic acetylcholine receptors and to the acetylcholine binding protein
    Svetoslav H Slavov
    Center for Heterocyclic Compounds, Department of Chemistry, University of Florida, Gainesville, FL 32611, USA
    Eur J Med Chem 45:2433-46. 2010

Collaborators

Detail Information

Publications20

  1. ncbi request reprint Alzheimer's drug design based upon an invertebrate toxin (anabaseine) which is a potent nicotinic receptor agonist
    W R Kem
    Department of Pharmacology and Therapeutics, University of Florida College of Medicine, Gainesville 32610 0267, USA
    Invert Neurosci 3:251-9. 1997
    ..The chemical and pharmacological properties of GTS-21 are compared with those of the initial lead compound, anabaseine...
  2. ncbi request reprint The brain alpha7 nicotinic receptor may be an important therapeutic target for the treatment of Alzheimer's disease: studies with DMXBA (GTS-21)
    W R Kem
    Department of Pharmacology and Experimental Therapeutics, University of Florida College of Medicine, Gainesville 32610 0267, USA
    Behav Brain Res 113:169-81. 2000
    ..Thus, some of the physiological and behavioral effects of GTS-21 may be due to the actions of this primary metabolite...
  3. ncbi request reprint Inhibition of barnacle larval settlement and crustacean toxicity of some hoplonemertine pyridyl alkaloids
    William R Kem
    Department of Pharmacology and Therapeutics, University of Florida College of Medicine, Gainesville, FL 32610 0267, USA
    Biomol Eng 20:355-61. 2003
    ..Nemertelline inhibited barnacle settlement at concentrations similar to 2,3'-BP but was 136-fold less toxic when injected into crayfish. Thus, certain bipyridyls and tetrapyridyls may be useful anti-fouling additives...
  4. ncbi request reprint Hydroxy metabolites of the Alzheimer's drug candidate 3-[(2,4-dimethoxy)benzylidene]-anabaseine dihydrochloride (GTS-21): their molecular properties, interactions with brain nicotinic receptors, and brain penetration
    William R Kem
    Department of Pharmacology and Therapeutics, College of Medicine, University of Florida, Gainesville, FL 32610 0267, USA
    Mol Pharmacol 65:56-67. 2004
    ..Benzylidene anabaseines pharmacologically similar to the hydroxy metabolites, but which enter the brain more readily, may provide greater stimulation of alpha7 receptors in the whole organism...
  5. ncbi request reprint Nicotinic receptor inhibition by Tetraponera ant alkaloids
    William R Kem
    Department of Pharmacology and Therapeutics, University of Florida College of Medicine, Gainesville, Florida 32610 0267, USA
    Cell Mol Neurobiol 24:535-51. 2004
    ..5. We conclude that the tetraponerines act at a site on nAChRs different from the ACh binding site which is probably located within the ion channel...
  6. pmc Activation and desensitization of nicotinic alpha7-type acetylcholine receptors by benzylidene anabaseines and nicotine
    Roger L Papke
    Department of Pharmacology and Therapeutics, University of Florida College of Medicine, Gainesville, FL 32610 0267, USA
    J Pharmacol Exp Ther 329:791-807. 2009
    ....
  7. pmc Positive modulation of alpha7 nAChR responses in rat hippocampal interneurons to full agonists and the alpha7-selective partial agonists, 4OH-GTS-21 and S 24795
    Gretchen Y López-Hernández
    Department of Pharmacology and Therapeutics, University of Florida, College of Medicine, Gainesville, FL 32610 0267, USA
    Neuropharmacology 56:821-30. 2009
    ..We demonstrated that the potentiation of alpha7 nAChR response would depend on the nature and the effective concentration of the agonist involved and its particular interaction with the positive modulator...
  8. pmc Point-to-point ligand-receptor interactions across the subunit interface modulate the induction and stabilization of conformational states of alpha7 nAChR by benzylidene anabaseines
    Matthew D Isaacson
    Department of Pharmacology and Therapeutics, University of Florida College of Medicine, P O Box 100267, Gainesville, FL 32610, United States
    Biochem Pharmacol 85:817-28. 2013
    ..These results indicate that the fine-tuning of agonists for specific interaction with S36 can facilitate the development of therapeutics with targeted effects on ion channel desensitization properties and conformational state stability...
  9. ncbi request reprint The structural basis for GTS-21 selectivity between human and rat nicotinic alpha7 receptors
    Clare Stokes
    Department of Pharmacology and Therapeutics, P O Box 100267, 1600 SW Archer Rd, University of Florida, College of Medicine, Gainesville, FL 32610, USA
    Mol Pharmacol 66:14-24. 2004
    ..Specific features in the agonist molecule itself are also identified that interact with these structural features of the receptor agonist binding site...
  10. doi request reprint A computational study of the binding of 3-(arylidene) anabaseines to two major brain nicotinic acetylcholine receptors and to the acetylcholine binding protein
    Svetoslav H Slavov
    Center for Heterocyclic Compounds, Department of Chemistry, University of Florida, Gainesville, FL 32611, USA
    Eur J Med Chem 45:2433-46. 2010
    ..5A away from the benzylidene ring at position 4 seem optimal for enhancing binding affinity to the alpha7 nAChR...
  11. doi request reprint Nicotine analog inhibition of nicotine self-administration in rats
    Neil E Rowland
    Department of Psychology, University of Florida, Gainesville, FL 32611 2250, USA
    Psychopharmacology (Berl) 199:605-13. 2008
    ..Partial agonists and antagonists of addictive drugs have been useful in the treatment of dependence...
  12. ncbi request reprint DMXB, an alpha7 nicotinic agonist, normalizes auditory gating in isolation-reared rats
    Heidi C O'Neill
    Department of Psychiatry C268 71, University of Colorado Health Sciences Center, 4200 East 9th Avenue, Denver, CO 80262, USA
    Psychopharmacology (Berl) 169:332-9. 2003
    ..3-(2,4)-Dimethoxybenzylidine anabaseine (DMXB; also known as GTS-21) is such an agonist and has shown efficacy in mice both orally and intraperitoneally...
  13. pmc Initial phase 2 trial of a nicotinic agonist in schizophrenia
    Robert Freedman
    Department of Psychiatry, Denver VA Medical Center and University of Colorado, Denver, CO 80262, USA
    Am J Psychiatry 165:1040-7. 2008
    ..The agent 3-(2,4-dimethoxybenzylidene) anabaseine (DMXB-A) is a partial alpha(7)-nicotinic agonist and can be taken orally. A phase 1 trial showed evidence for cognitive enhancement in schizophrenia...
  14. pmc Spectroscopic analysis of benzylidene anabaseine complexes with acetylcholine binding proteins as models for ligand-nicotinic receptor interactions
    Todd T Talley
    Department of Pharmacology, University of California, San Diego, La Jolla, California 92093 0636, USA
    Biochemistry 45:8894-902. 2006
    ....
  15. ncbi request reprint Proof-of-concept trial of an alpha7 nicotinic agonist in schizophrenia
    Ann Olincy
    Department of Veterans Affairs Schizophrenia Research Center, Denver, Colorado, USA
    Arch Gen Psychiatry 63:630-8. 2006
    ....
  16. ncbi request reprint N-terminal domains in mouse and human 5-hydroxytryptamine3A receptors confer partial agonist and antagonist properties to benzylidene analogs of anabaseine
    Ran Zhang
    Dept of Pharmacology and Neuroscience, University of North Texas Health Science Center, 3500 Camp Bowie Blvd, Ft Worth, TX 76107 2699, USA
    J Pharmacol Exp Ther 317:1276-84. 2006
    ..Thus, amino acids present in the distal one-third of the N terminus of mouse and human 5-HT3A receptors are necessary and sufficient to confer partial agonist or antagonist properties of 2-OHMBA...
  17. ncbi request reprint Unique general anesthetic binding sites within distinct conformational states of the nicotinic acetylcholine receptor
    Hugo R Arias
    Department of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, Pomona, California 91766, USA
    Int Rev Neurobiol 54:1-50. 2003
    ..GAs inhibition channels by at least two mechanisms, an open-channel-blocking and/or an allosteric mechanism. 7. Certain GAs may inhibit AChR function by competing for the agonist binding sites or by augmenting the desensitization rate...
  18. ncbi request reprint Alpha-7 nicotinic receptor agonists: potential new candidates for the treatment of schizophrenia
    Laura F Martin
    Department of Psychiatry, Department of Veterans Affairs and University of Colorado Health Sciences Center, 4200 East Ninth Avenue, C268 71, Denver, CO 80262, USA
    Psychopharmacology (Berl) 174:54-64. 2004
    ..This inhibitory process, which involves the alpha(7) nicotinic receptor mediated release of gamma-aminobutyric acid (GABA) by hippocampal interneurons, represents a potential new target for therapeutic intervention in schizophrenia...
  19. ncbi request reprint Relative toxicities and neuromuscular nicotinic receptor agonistic potencies of anabasine enantiomers and anabaseine
    Stephen T Lee
    Poisonous Plant Research Laboratory, Agricultural Research Service, United States Department of Agriculture, 1150 E 1400 N, Logan, UT 84341, USA
    Neurotoxicol Teratol 28:220-8. 2006
    ..The relative agonistic potencies of these three alkaloids on human fetal nicotinic neuromuscular receptors were of the same rank order: anabaseine>>R-anabasine>S-anabasine...
  20. ncbi request reprint Isolation and characterisation of a cytolytic protein from mucus secretions of the Antarctic heteronemertine Parborlasia corrugatus
    Sabina Berne
    Department of Biology, Biotechnical Faculty, University of Ljubljana, Ljubljana 1000, Slovenia
    Toxicon 41:483-91. 2003
    ....