Research Topics
| William R KemSummaryAffiliation: University of Florida Country: USA Publications
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Publications
Alzheimer's drug design based upon an invertebrate toxin (anabaseine) which is a potent nicotinic receptor agonistW 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...- 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 penetrationWilliam 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... - Inhibition of barnacle larval settlement and crustacean toxicity of some hoplonemertine pyridyl alkaloidsWilliam 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... - 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... - Nicotinic receptor inhibition by Tetraponera ant alkaloidsWilliam 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... 
Activation and desensitization of nicotinic alpha7-type acetylcholine receptors by benzylidene anabaseines and nicotineRoger 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....- Positive modulation of alpha7 nAChR responses in rat hippocampal interneurons to full agonists and the alpha7-selective partial agonists, 4OH-GTS-21 and S 24795Gretchen 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... 
A computational study of the binding of 3-(arylidene) anabaseines to two major brain nicotinic acetylcholine receptors and to the acetylcholine binding proteinSvetoslav 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...- The structural basis for GTS-21 selectivity between human and rat nicotinic alpha7 receptorsClare 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... - Nicotine analog inhibition of nicotine self-administration in ratsNeil 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... - Point-to-point ligand-receptor interactions across the subunit interface modulate the induction and stabilization of conformational states of alpha7 nAChR by benzylidene anabaseinesMatthew 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... - N-terminal domains in mouse and human 5-hydroxytryptamine3A receptors confer partial agonist and antagonist properties to benzylidene analogs of anabaseineRan 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... - Proof-of-concept trial of an alpha7 nicotinic agonist in schizophreniaAnn Olincy
Department of Veterans Affairs Schizophrenia Research Center, Denver, Colorado, USA
Arch Gen Psychiatry 63:630-8. 2006.... - Spectroscopic analysis of benzylidene anabaseine complexes with acetylcholine binding proteins as models for ligand-nicotinic receptor interactionsTodd T Talley
Department of Pharmacology, University of California, San Diego, La Jolla, California 92093-0636, USA
Biochemistry 45:8894-902. 2006.... - Initial phase 2 trial of a nicotinic agonist in schizophreniaRobert 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... - Alpha-7 nicotinic receptor agonists: potential new candidates for the treatment of schizophreniaLaura 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... - Unique general anesthetic binding sites within distinct conformational states of the nicotinic acetylcholine receptorHugo 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... - DMXB, an alpha7 nicotinic agonist, normalizes auditory gating in isolation-reared ratsKate Rieger
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..The results in the isolation-reared rats are in concert with previous studies which found similar improvement in auditory gating following administration of DMXB to DBA mice, the only differences being in the duration of the effect... - Relative toxicities and neuromuscular nicotinic receptor agonistic potencies of anabasine enantiomers and anabaseineStephen 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... - Isolation and characterisation of a cytolytic protein from mucus secretions of the Antarctic heteronemertine Parborlasia corrugatusSabina Berne
Department of Biology, Biotechnical Faculty, University of Ljubljana, Ljubljana 1000, Slovenia
Toxicon 41:483-91. 2003....