Linda Dwoskin

Summary

Affiliation: University of Kentucky
Country: USA

Publications

  1. pmc N,N'-Alkane-diyl-bis-3-picoliniums as nicotinic receptor antagonists: inhibition of nicotine-evoked dopamine release and hyperactivity
    Linda P Dwoskin
    Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536 0082, USA
    J Pharmacol Exp Ther 326:563-76. 2008
  2. doi request reprint Nicotinic receptor-based therapeutics and candidates for smoking cessation
    Linda P Dwoskin
    Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA
    Biochem Pharmacol 78:732-43. 2009
  3. pmc Discovery of a novel nicotinic receptor antagonist for the treatment of nicotine addiction: 1-(3-Picolinium)-12-triethylammonium-dodecane dibromide (TMPD)
    Linda P Dwoskin
    Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536 0082, USA
    Biochem Pharmacol 74:1271-82. 2007
  4. ncbi request reprint Review of the pharmacology and clinical profile of bupropion, an antidepressant and tobacco use cessation agent
    Linda P Dwoskin
    Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536 0082, USA
    CNS Drug Rev 12:178-207. 2006
  5. ncbi request reprint Individual differences in response to novelty predict prefrontal cortex dopamine transporter function and cell surface expression
    Jun Zhu
    College of Pharmacy, University of Kentucky, 725 Rose Street, Lexington, KY 40536 0082, USA
    Eur J Neurosci 26:717-28. 2007
  6. pmc Introduction of unsaturation into the N-n-alkyl chain of the nicotinic receptor antagonists, NONI and NDNI: effect on affinity and selectivity
    Sangeetha P Sumithran
    College of Pharmacy, University of Kentucky, Lexington, KY 40536 0082, USA
    AAPS J 7:E201-17. 2005
  7. pmc Lobeline analogs with enhanced affinity and selectivity for plasmalemma and vesicular monoamine transporters
    Dennis K Miller
    College of Pharmacy, University of Kentucky, Lexington, KY, 40536 0082, USA
    J Pharmacol Exp Ther 310:1035-45. 2004
  8. ncbi request reprint Environmental enrichment enhances sensitization to GBR 12935-induced activity and decreases dopamine transporter function in the medial prefrontal cortex
    Jun Zhu
    College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA
    Behav Brain Res 148:107-17. 2004
  9. ncbi request reprint Reboxetine: functional inhibition of monoamine transporters and nicotinic acetylcholine receptors
    Dennis K Miller
    College of Pharmacy, University of Kentucky, Lexington, KY 40536 0082, USA
    J Pharmacol Exp Ther 302:687-95. 2002
  10. pmc Nicotine increases dopamine transporter function in rat striatum through a trafficking-independent mechanism
    Lisa S Middleton
    University of Kentucky, Department of Pharmaceutical Sciences, College of Pharmacy, Lexington, Kentucky 40536 0082, USA
    Eur J Pharmacol 554:128-36. 2007

Collaborators

Detail Information

Publications78

  1. pmc N,N'-Alkane-diyl-bis-3-picoliniums as nicotinic receptor antagonists: inhibition of nicotine-evoked dopamine release and hyperactivity
    Linda P Dwoskin
    Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536 0082, USA
    J Pharmacol Exp Ther 326:563-76. 2008
    ..Further development of nAChR antagonists that inhibit nicotine-evoked DA release and penetrate brain to antagonize DA-mediated locomotor stimulant effects of nicotine as novel treatments for nicotine addiction is warranted...
  2. doi request reprint Nicotinic receptor-based therapeutics and candidates for smoking cessation
    Linda P Dwoskin
    Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA
    Biochem Pharmacol 78:732-43. 2009
    ..This review summarizes the currently available smoking cessation therapies and discusses emerging potential therapeutic approaches employing pharmacological agents which act as antagonists at nicotinic receptors...
  3. pmc Discovery of a novel nicotinic receptor antagonist for the treatment of nicotine addiction: 1-(3-Picolinium)-12-triethylammonium-dodecane dibromide (TMPD)
    Linda P Dwoskin
    Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536 0082, USA
    Biochem Pharmacol 74:1271-82. 2007
    ....
  4. ncbi request reprint Review of the pharmacology and clinical profile of bupropion, an antidepressant and tobacco use cessation agent
    Linda P Dwoskin
    Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536 0082, USA
    CNS Drug Rev 12:178-207. 2006
    ..Extensive hepatic metabolism of bupropion produces three pharmacologically active metabolites, which may contribute to its clinical profile...
  5. ncbi request reprint Individual differences in response to novelty predict prefrontal cortex dopamine transporter function and cell surface expression
    Jun Zhu
    College of Pharmacy, University of Kentucky, 725 Rose Street, Lexington, KY 40536 0082, USA
    Eur J Neurosci 26:717-28. 2007
    ....
  6. pmc Introduction of unsaturation into the N-n-alkyl chain of the nicotinic receptor antagonists, NONI and NDNI: effect on affinity and selectivity
    Sangeetha P Sumithran
    College of Pharmacy, University of Kentucky, Lexington, KY 40536 0082, USA
    AAPS J 7:E201-17. 2005
    ....
  7. pmc Lobeline analogs with enhanced affinity and selectivity for plasmalemma and vesicular monoamine transporters
    Dennis K Miller
    College of Pharmacy, University of Kentucky, Lexington, KY, 40536 0082, USA
    J Pharmacol Exp Ther 310:1035-45. 2004
    ....
  8. ncbi request reprint Environmental enrichment enhances sensitization to GBR 12935-induced activity and decreases dopamine transporter function in the medial prefrontal cortex
    Jun Zhu
    College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA
    Behav Brain Res 148:107-17. 2004
    ..These results suggest that EC-induced changes in activity may be due to decreased DAT function and decreased DA metabolism in the mPFC...
  9. ncbi request reprint Reboxetine: functional inhibition of monoamine transporters and nicotinic acetylcholine receptors
    Dennis K Miller
    College of Pharmacy, University of Kentucky, Lexington, KY 40536 0082, USA
    J Pharmacol Exp Ther 302:687-95. 2002
    ..Thus, in addition to inhibition of NET function, reboxetine inhibits nAChR function, suggesting that it may have potential as a smoking cessation agent...
  10. pmc Nicotine increases dopamine transporter function in rat striatum through a trafficking-independent mechanism
    Lisa S Middleton
    University of Kentucky, Department of Pharmaceutical Sciences, College of Pharmacy, Lexington, Kentucky 40536 0082, USA
    Eur J Pharmacol 554:128-36. 2007
    ..These results suggest that the nicotine-induced increase in dopamine uptake and clearance in striatum may occur via a trafficking-independent mechanism...
  11. ncbi request reprint bis-Azaaromatic quaternary ammonium analogues: ligands for alpha4beta2* and alpha7* subtypes of neuronal nicotinic receptors
    Joshua T Ayers
    Division of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536 0082, USA
    Bioorg Med Chem Lett 12:3067-71. 2002
    ....
  12. ncbi request reprint Bupropion inhibits nicotine-evoked [(3)H]overflow from rat striatal slices preloaded with [(3)H]dopamine and from rat hippocampal slices preloaded with [(3)H]norepinephrine
    Dennis K Miller
    College of Pharmacy, University of Kentucky, Lexington, KY 40536 0082, USA
    J Pharmacol Exp Ther 302:1113-22. 2002
    ..The combination of nAChR and transporter inhibition produced by bupropion may contribute to its clinical efficacy as a smoking cessation agent...
  13. ncbi request reprint Nornicotine inhibition of dopamine transporter function in striatum via nicotinic receptor activation
    Lisa S Middleton
    Department of Pharmaceutical Sciences, University of Kentucky, Lexington, Kentucky 40536, USA
    Synapse 61:157-65. 2007
    ..Understanding the actions of nornicotine in brain may have significance for emerging therapeutics and for the management of nicotine dependence...
  14. ncbi request reprint 3D-QSAR study of bis-azaaromatic quaternary ammonium analogs at the blood-brain barrier choline transporter
    Werner J Geldenhuys
    Department of Pharmaceutical Sciences, Texas Tech University Health Sciences Center, School of Pharmacy, 1300 S Coulter Dr, Amarillo, TX, 79106 1712, USA
    Bioorg Med Chem 13:4253-61. 2005
    ..506 and the non-cross-validated r2 was 0.804. This new model was able to better predict BBB-choline transporter affinity of hemicholinium-3 (predicted 65 microM, actual 54 microM), when compared to an earlier model (predicted 316 microM)...
  15. pmc Lobelane inhibits methamphetamine-evoked dopamine release via inhibition of the vesicular monoamine transporter-2
    Justin R Nickell
    Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536 0082, USA
    J Pharmacol Exp Ther 332:612-21. 2010
    ..The current results reveal that lobelane, a selective VMAT2 inhibitor, inhibits methamphetamine-evoked DA release and is a promising lead for the development of a pharmacotherapeutic for methamphetamine abuse...
  16. pmc The novel nicotinic receptor antagonist, N,N'-dodecane-1,12-diyl-bis-3-picolinium dibromide (bPiDDB), inhibits nicotine-evoked [(3)H]norepinephrine overflow from rat hippocampal slices
    Andrew M Smith
    Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536 0082, United States
    Biochem Pharmacol 78:889-97. 2009
    ..Thus, bPiDDB was 200-fold more potent inhibiting nAChRs mediating nicotine-evoked [(3)H]DA release from striatum than those mediating nicotine-evoked [(3)H]NE release from hippocampus...
  17. pmc Lobelane decreases methamphetamine self-administration in rats
    Nichole M Neugebauer
    Department of Psychology, University of Kentucky, Lexington, KY 40536, USA
    Eur J Pharmacol 571:33-8. 2007
    ....
  18. pmc Lobelane analogues as novel ligands for the vesicular monoamine transporter-2
    Guangrong Zheng
    College of Pharmacy, University of Kentucky, Rose Street, Lexington, KY 40536 0082, USA
    Bioorg Med Chem 13:3899-909. 2005
    ..The most potent analogues in this series were the cis-2,6-piperidino analogues, 25b, 27b, 28b, and 30b, with K(i) values ranging from 430 to 580 nM...
  19. ncbi request reprint Carrier-mediated transport of the quaternary ammonium neuronal nicotinic receptor antagonist n,n'-dodecylbispicolinium dibromide at the blood-brain barrier
    Paul R Lockman
    Department of Pharmaceutical Sciences, Texas Tech University Health Sciences Center, 1300 S Coulter Dr, Amarillo, TX 79106 1712, USA
    J Pharmacol Exp Ther 324:244-50. 2008
    ..The current results suggest that bPiDDB uses the BBB choline transporter for approximately 90% of its permeation into brain, and they demonstrate the carrier-mediated BBB penetration of a novel bisquaternary ammonium nAChR antagonist...
  20. pmc Modeling multiple species of nicotine and deschloroepibatidine interacting with alpha4beta2 nicotinic acetylcholine receptor: from microscopic binding to phenomenological binding affinity
    Xiaoqin Huang
    Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 725 Rose Street, Lexington, KY 40536, USA
    J Am Chem Soc 127:14401-14. 2005
    ....
  21. pmc The novel nicotinic receptor antagonist N,N'-dodecane-1,12-diyl-bis-3-picolinium dibromide decreases nicotine-induced dopamine metabolism in rat nucleus accumbens
    Shafiqur Rahman
    Center for Drug Abuse Research Translation, University of Kentucky, Lexington, KY 40506, USA
    Eur J Pharmacol 601:103-5. 2008
    ..These results indicate that bPiDDB inhibits the nicotine-induced increase in DOPAC in reward-relevant brain region targeting nicotinic acetylcholine receptors...
  22. ncbi request reprint N-n-alkylpyridinium analogs, a novel class of nicotinic receptor antagonists: selective inhibition of nicotine-evoked [3H] dopamine overflow from superfused rat striatal slices
    Vladimir P Grinevich
    College of Pharmacy, University of Kentucky, Lexington, KY 40536 0082, USA
    J Pharmacol Exp Ther 306:1011-20. 2003
    ....
  23. ncbi request reprint Active transport of high-affinity choline and nicotine analogs into the central nervous system by the blood-brain barrier choline transporter
    David D Allen
    Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University HSC, Amarillo, Texas 79106, USA
    J Pharmacol Exp Ther 304:1268-74. 2003
    ..Thus, NONI may have utility as a smoking cessation agent, given its ability to inhibit nAChRs mediating nicotine-evoked dopamine release centrally, and to be distributed to brain via the BBB choline transporter...
  24. ncbi request reprint N-n-alkylnicotinium analogs, a novel class of nicotinic receptor antagonist: inhibition of S(-)-nicotine-evoked [(3)H]dopamine overflow from superfused rat striatal slices
    Lincoln H Wilkins
    College of Pharmacy, University of Kentucky, Lexington, KY 40536 0082, USA
    J Pharmacol Exp Ther 301:1088-96. 2002
    ..2 nM). Thus, modification of the S(-)-nicotine molecule converts this agonist into an antagonist at nAChRs, mediating S(-)-nicotine-evoked DA release in striatum...
  25. ncbi request reprint Modeling subtype-selective agonists binding with alpha4beta2 and alpha7 nicotinic acetylcholine receptors: effects of local binding and long-range electrostatic interactions
    Xiaoqin Huang
    Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 725 Rose Street, Lexington, KY 40536, USA
    J Med Chem 49:7661-74. 2006
    ..The fundamental insights obtained in the present study should be valuable for future rational design of potential therapeutic agents targeted to specific nAChR subtypes...
  26. pmc Repeated nicotine administration robustly increases bPiDDB inhibitory potency at alpha6beta2-containing nicotinic receptors mediating nicotine-evoked dopamine release
    Andrew M Smith
    Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA
    Biochem Pharmacol 80:402-9. 2010
    ..Therefore, bPiDDB and r-bPiDDB appear to target different alpha6beta2-containing nAChR subtypes...
  27. ncbi request reprint The effects of a novel nicotinic receptor antagonist N,N-dodecane-1,12-diyl-bis-3-picolinium dibromide (bPiDDB) on acute and repeated nicotine-induced increases in extracellular dopamine in rat nucleus accumbens
    Shafiqur Rahman
    Center for Drug Abuse Research Translation, University of Kentucky, Lexington, KY 40506, USA
    Neuropharmacology 52:755-63. 2007
    ....
  28. pmc Lobeline esters as novel ligands for neuronal nicotinic acetylcholine receptors and neurotransmitter transporters
    Marhaba Hojahmat
    College of Pharmacy, University of Kentucky, Rose Street, Lexington, KY 40536 0082, USA
    Bioorg Med Chem 18:640-9. 2010
    ..5-fold selectivity for VMAT2 over alpha4beta2 nAChRs. Thus, esterification of the lobeline molecule may be a useful structural modification for the development of lobeline analogs with improved selectivity at VMAT2...
  29. ncbi request reprint Tris-azaaromatic quaternary ammonium salts: Novel templates as antagonists at nicotinic receptors mediating nicotine-evoked dopamine release
    Guangrong Zheng
    Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536 0082, USA
    Bioorg Med Chem Lett 17:6701-6. 2007
    ..2 nM and I(max) of 67%...
  30. ncbi request reprint Effect of bupropion on nicotine self-administration in rats
    Anthony S Rauhut
    Department of Psychology, University of Kentucky, Lexington, KY 40536, USA
    Psychopharmacology (Berl) 169:1-9. 2003
    ..To determine the specificity of bupropion-induced changes in nicotine self-administration, the ability of bupropion to alter sucrose-maintained responding or amphetamine self-administration was determined...
  31. ncbi request reprint Bis-azaaromatic quaternary ammonium salts as antagonists at nicotinic receptors mediating nicotine-evoked dopamine release: An investigation of binding conformation
    Guangrong Zheng
    Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536 0082, USA
    Bioorg Med Chem Lett 17:6734-8. 2007
    ....
  32. pmc Nicotinic receptor activation increases [3H]dopamine uptake and cell surface expression of dopamine transporters in rat prefrontal cortex
    Jun Zhu
    College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA
    J Pharmacol Exp Ther 328:931-9. 2009
    ..Thus, results from the present study suggest that the nicotine-induced increases in DAT function and cell surface expression in PFC may mediate some of the behavioral effects of nicotine...
  33. doi request reprint QSAR study on maximal inhibition (Imax) of quaternary ammonium antagonists for S-(-)-nicotine-evoked dopamine release from dopaminergic nerve terminals in rat striatum
    Fang Zheng
    Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536, United States
    Bioorg Med Chem 17:4477-85. 2009
    ....
  34. pmc bis-Pyridinium cyclophanes: novel ligands with high affinity for the blood-brain barrier choline transporter
    Zhenfa Zhang
    Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA
    Bioorg Med Chem Lett 18:5622-5. 2008
    ..8 microM and 1.4 microM, respectively, and constitute some of the most potent BBB choline transporter ligands reported...
  35. pmc Design, synthesis and interaction at the vesicular monoamine transporter-2 of lobeline analogs: potential pharmacotherapies for the treatment of psychostimulant abuse
    Peter A Crooks
    Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, 40536 0082, USA
    Curr Top Med Chem 11:1103-27. 2011
    ....
  36. pmc Quinlobelane: a water-soluble lobelane analogue and inhibitor of VMAT2
    Ashish P Vartak
    Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA
    Bioorg Med Chem Lett 20:3584-7. 2010
    ..The quinolyl group was the only replacement for the phenyl group in lobelane that retained VMAT2 inhibition...
  37. pmc Novel bis-2,2,6,6-tetramethylpiperidine (bis-TMP) and bis-mecamylamine antagonists at neuronal nicotinic receptors mediating nicotine-evoked dopamine release
    Zhenfa Zhang
    College of Pharmacy, Department of Pharmaceutical Sciences, University of Kentucky, Lexington, KY 40536 0082, USA
    Bioorg Med Chem Lett 20:1420-3. 2010
    ....
  38. ncbi request reprint A novel mechanism of action and potential use for lobeline as a treatment for psychostimulant abuse
    Linda P Dwoskin
    College of Pharmacy, University of Kentucky, Rose Street, Lexington, KY 40536 0082, USA
    Biochem Pharmacol 63:89-98. 2002
    ..The development of lobeline and lobeline analogs with targeted selectivity at VMAT2 represents a novel class of therapeutic agents having good potential as efficacious treatments for methamphetamine abuse...
  39. ncbi request reprint Environmental enrichment decreases cell surface expression of the dopamine transporter in rat medial prefrontal cortex
    Jun Zhu
    College of Pharmacy, Univeristy of Kentucky, Lexington, Kentucky 40536 0082, USA
    J Neurochem 93:1434-43. 2005
    ....
  40. ncbi request reprint Subtype-selective nicotinic receptor antagonists: potential as tobacco use cessation agents
    Linda P Dwoskin
    Division of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536 0082, USA
    Bioorg Med Chem Lett 14:1863-7. 2004
    ..bPiDDB represents the current lead compound for development as a tobacco use cessation agent...
  41. ncbi request reprint Nicotinic receptor modulation of dopamine transporter function in rat striatum and medial prefrontal cortex
    Lisa S Middleton
    College of Pharmacy, University of Kentucky, Lexington, Kentucky 40536, USA
    J Pharmacol Exp Ther 308:367-77. 2004
    ..Thus, nicotine enhances DA clearance in striatum and mPFC in a mecamylamine-sensitive manner, indicating that nAChRs modulate DAT function in these brain regions...
  42. ncbi request reprint A pilot study of plasma caffeine concentrations in a US sample of smoker and nonsmoker volunteers
    Jose de Leon
    University of Kentucky UK Mental Health Research Center at Eastern State Hospital, 627 West Fourth Street, Lexington, KY 40508, USA
    Prog Neuropsychopharmacol Biol Psychiatry 27:165-71. 2003
    ..Additional studies are needed to replicate the model. This model may help epidemiologists to correct for the effects of smoking on caffeine intake and pharmacologists to screen for the activity of CYP1A2...
  43. ncbi request reprint Development of subtype-selective ligands as antagonists at nicotinic receptors mediating nicotine-evoked dopamine release
    Peter A Crooks
    Division of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536 0082, USA
    Bioorg Med Chem Lett 14:1869-74. 2004
    ..Conformationally restricted analogues exhibit both high affinity and selectivity at this site, and are able to access the brain due to their ability to act as substrates for the blood-brain barrier choline transporter...
  44. ncbi request reprint N-n-alkylnicotinium analogs, a novel class of nicotinic receptor antagonists: interaction with alpha4beta2* and alpha7* neuronal nicotinic receptors
    Lincoln H Wilkins
    College of Pharmacy, University of Kentucky, Lexington, Kentucky 40536 0082, USA
    J Pharmacol Exp Ther 304:400-10. 2003
    ....
  45. ncbi request reprint Lobeline attenuates locomotor stimulation induced by repeated nicotine administration in rats
    Dennis K Miller
    College of Pharmacy, University of Kentucky, Rose Street, Lexington, KY 40536 0082, USA
    Pharmacol Biochem Behav 74:279-86. 2003
    ....
  46. ncbi request reprint Lobeline does not serve as a reinforcer in rats
    Steven B Harrod
    Department of Psychology, University of Kentucky, 115 Kastle Hall, Lexington, KY 40506 0044, USA
    Psychopharmacology (Berl) 165:397-404. 2003
    ..Previous results demonstrated that pretreatment with lobeline attenuates d-methamphetamine self-administration in rats...
  47. ncbi request reprint Reboxetine: attenuation of intravenous nicotine self-administration in rats
    Anthony S Rauhut
    Department of Psychology, University of Kentucky, Lexington, KY 40536 0082, USA
    J Pharmacol Exp Ther 303:664-72. 2002
    ..The reboxetine-induced decrease in nicotine self-administration and sucrose-maintained responding may be the result of inhibition of norepinephrine transporters and/or neuronal nicotinic receptor function...
  48. ncbi request reprint Total cotinine in plasma: a stable biomarker for exposure to tobacco smoke
    Jose de Leon
    University of Kentucky Mental Health Research Center at Eastern State Hospital, Lexington, 40508, USA
    J Clin Psychopharmacol 22:496-501. 2002
    ..New studies of total cotinine in plasma using more than two blood collections during the day are needed to definitively establish that it is a stable biomarker for epidemiological studies...
  49. ncbi request reprint QSAR modeling of mono- and bis-quaternary ammonium salts that act as antagonists at neuronal nicotinic acetylcholine receptors mediating dopamine release
    Fang Zheng
    Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536 0082, USA
    Bioorg Med Chem 14:3017-37. 2006
    ..1 microM at nAChR subtypes responsible for mediating nicotine-evoked dopamine release, demonstrating that the ANN QSAR model is a valuable aid to drug discovery...
  50. ncbi request reprint Mitochondrial toxin inhibition of [(3)H]dopamine uptake into rat striatal synaptosomes
    William F Maragos
    Department of Neurology, Kentucky Clinic, Room L 445, University of Kentucky Medical Center, Lexington, KY 40536, USA
    Biochem Pharmacol 63:1499-505. 2002
    ..e. noncompetitive inhibition of the DAT...
  51. ncbi request reprint Des-keto lobeline analogs with increased potency and selectivity at dopamine and serotonin transporters
    Guangrong Zheng
    College of Pharmacy, University of Kentucky, Lexington, 40536 0082, USA
    Bioorg Med Chem Lett 16:5018-21. 2006
    ..The enantiomers 8R-hydroxylobel-9-ene (3a) and 10S-hydroxylobel-7-ene (3c) exhibited high potency and selectivity at SERT and DAT, respectively...
  52. pmc Tetrakis-azaaromatic quaternary ammonium salts: novel subtype-selective antagonists at neuronal nicotinic receptors that mediate nicotine-evoked dopamine release
    Zhenfa Zhang
    Department of Pharmaceutical Sciences, University of Kentucky, Lexington, KY 40536 0082, USA
    Bioorg Med Chem Lett 18:5753-7. 2008
    ..Three tetrakis analogs, 11j, 11f, and 11g, were identified as potent (IC(50)=3, 28 and 56nM, respectively) antagonists at these receptors. These compounds represent a novel structural class of nicotinic receptor antagonists...
  53. pmc Synthesis and evaluation of a series of homologues of lobelane at the vesicular monoamine transporter-2
    Guangrong Zheng
    Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Rose Street, Lexington, KY 40536 0082, USA
    Bioorg Med Chem Lett 18:6509-12. 2008
    ..These results indicate that the intramolecular distances between the piperidine ring and two phenyl rings in lobelane analogues are an important criterion for retention of high affinity at VMAT2...
  54. pmc Pyrrolidine analogues of lobelane: relationship of affinity for the dihydrotetrabenazine binding site with function of the vesicular monoamine transporter 2 (VMAT2)
    Ashish P Vartak
    Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 725 Rose Street, Lexington, Kentucky 40536, USA
    J Med Chem 52:7878-82. 2009
    ..e., the DTBZ binding site and an alternative site on VMAT2 to inhibit transporter function...
  55. pmc Computational neural network analysis of the affinity of N-n-alkylnicotinium salts for the alpha4beta2* nicotinic acetylcholine receptor
    Fang Zheng
    Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, Kentucky, USA
    J Enzyme Inhib Med Chem 24:157-68. 2009
    ..The generated neural network model with the 85 molecule training set may also be of value for future predictions of K(i) values for new virtual compounds, which can then be identified, subsequently synthesized, and tested experimentally...
  56. pmc Computational neural network analysis of the affinity of lobeline and tetrabenazine analogs for the vesicular monoamine transporter-2
    Fang Zheng
    Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA
    Bioorg Med Chem 15:2975-92. 2007
    ..The developed models are expected to be useful in the rational design of new chemical entities as ligands of VMAT2 and for directing synthesis of new molecules in the future...
  57. pmc Synthesis and evaluation of a series of tropane analogues as novel vesicular monoamine transporter-2 ligands
    Guangrong Zheng
    College of Pharmacy, University of Kentucky, Lexington, KY 40536 0082, USA
    Bioorg Med Chem Lett 15:4463-6. 2005
    ..The trop-2-ene analogues 4a and 4b exhibited good affinity and high selectivity for VMAT2...
  58. ncbi request reprint Identification and synthesis of novel alkaloids from the root system of Nicotiana tabacum: affinity for neuronal nicotinic acetylcholine receptors
    Xiaochen Wei
    Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA
    Life Sci 78:495-505. 2005
    ..The results also demonstrate that these compounds act as antagonists at nAChRs mediating nicotine-evoked dopamine release from rat striatum...
  59. pmc The promiscuity of the dopamine transporter: implications for the kinetic analysis of [3H]serotonin uptake in rat hippocampal and striatal synaptosomes
    Seth D Norrholm
    College of Pharmacy, Department of Pharmaceutical Sciences, University of Kentucky, Lexington, KY 40536 0082, USA
    Neuropharmacology 53:982-9. 2007
    ..These findings have important implications regarding the analysis of monoaminergic reuptake in brain regions exhibiting heterogeneous transporter expression...
  60. pmc N-n-alkylnicotinium analogs, a novel class of antagonists at alpha 4 beta 2* nicotinic acetylcholine receptors: inhibition of S(-)-nicotine-evoked 86Rb+ efflux from rat thalamic synaptosomes
    Lincoln H Wilkins
    College of Pharmacy, University of Kentucky, Lexington, KY 40536 0082, USA
    AAPS J 7:E922-30. 2005
    ..Thus, NDNI is a competitive, selective antagonist at alpha4beta2* nAChRs...
  61. pmc Pharmacokinetics of the novel nicotinic receptor antagonist N,N'-dodecane-1,12-diyl-bis-3-picolinium dibromide in the rat
    Zaineb A Fadhel Albayati
    Department of Pharmaceutical Sciences, College of Pharmacy, Lexington, KY 40536 0082, USA
    Drug Metab Dispos 36:2024-9. 2008
    ....
  62. pmc Predictive screening model for potential vector-mediated transport of cationic substrates at the blood-brain barrier choline transporter
    Werner J Geldenhuys
    Department of Pharmaceutical Sciences, Texas Tech University Health Sciences Center, School of Pharmacy, Amarillo, TX 79106 1712, USA
    Bioorg Med Chem Lett 20:870-7. 2010
    ....
  63. pmc meso-Transdiene analogs inhibit vesicular monoamine transporter-2 function and methamphetamine-evoked dopamine release
    David B Horton
    Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536 0082, USA
    J Pharmacol Exp Ther 336:940-51. 2011
    ....
  64. pmc Phenyl ring-substituted lobelane analogs: inhibition of [³H]dopamine uptake at the vesicular monoamine transporter-2
    Justin R Nickell
    Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA
    J Pharmacol Exp Ther 336:724-33. 2011
    ..Thus, modification of the lobelane molecule affords potent, selective inhibitors of VMAT2 function and reveals two distinct pharmacological targets on VMAT2...
  65. pmc Novel N-1,2-dihydroxypropyl analogs of lobelane inhibit vesicular monoamine transporter-2 function and methamphetamine-evoked dopamine release
    David B Horton
    Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, Kentucky 40536 0082, USA
    J Pharmacol Exp Ther 339:286-97. 2011
    ..Thus, the pharmacophore for VMAT2 inhibition accommodates the N-1,2-diol moiety, which improves drug-likeness and enhances the potential for the development of these clinical candidates as treatments for methamphetamine abuse...
  66. ncbi request reprint Plasma cotinine, 3'-hydroxycotinine, and their glucuronides in white and black smokers
    Jose de Leon
    J Clin Psychopharmacol 23:209-11. 2003
  67. ncbi request reprint Effects of environmental enrichment on behavior and dopamine transporter function in medial prefrontal cortex in adult rats prenatally treated with cocaine
    Nichole M Neugebauer
    Department of Psychology, University of Massachusetts, Boston, MA 02125, USA
    Brain Res Dev Brain Res 153:213-23. 2004
    ....
  68. pmc The characterization of a novel rigid nicotine analog with alpha7-selective nAChR agonist activity and modulation of agonist properties by boron inclusion
    Roger L Papke
    University of Florida, College of Medicine, 1600 SW Archer Road, Gainesville, FL 32610, USA
    Bioorg Med Chem Lett 15:3874-80. 2005
    ....
  69. ncbi request reprint Tolerance does not develop to the decrease in nicotine self-administration produced by repeated bupropion administration
    Anthony S Rauhut
    Department of Psychology, Dickinson College, Carlisle, PA 17013, USA
    Nicotine Tob Res 7:901-7. 2005
    ..These results indicate that the rat nicotine self-administration paradigm is a useful animal model for assessing smoking cessation pharmacotherapies...
  70. pmc Defunctionalized lobeline analogues: structure-activity of novel ligands for the vesicular monoamine transporter
    Guangrong Zheng
    College of Pharmacy, University of Kentucky, Lexington, Kentucky 40536 0082, USA
    J Med Chem 48:5551-60. 2005
    ....
  71. ncbi request reprint The pharmacological activity of nicotine and nornicotine on nAChRs subtypes: relevance to nicotine dependence and drug discovery
    Roger L Papke
    Pharmacology and Therapeutics, University of Florida, College of Medicine, Gainesville, Florida 32610, USA
    J Neurochem 101:160-7. 2007
    ..Thus, understanding the actions of nornicotine in the brain may have significance for both emerging therapeutics and the management of nicotine dependence...
  72. pmc N,N-disubstituted piperazines: synthesis and affinities at alpha4beta2(*) and alpha7(*) neuronal nicotinic acetylcholine receptors
    Jianhong Chen
    Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 294 Tai Yuan Road, China
    Bioorg Med Chem Lett 13:97-100. 2003
    ..Thus, linking together a pyridine pi-system and a cyclic amine moiety via a piperazine ring affords compounds with low affinity, but good selectivity for alpha4beta2(*) nicotinic receptors...
  73. pmc Extending the analysis of nicotinic receptor antagonists with the study of alpha6 nicotinic receptor subunit chimeras
    Roger L Papke
    Department of Pharmacology and Therapeutics, University of Florida, College of Medicine, P O Box 100267, JHMHSC, 1600 SW Archer Road, Gainesville, FL 32610 0267, USA
    Neuropharmacology 54:1189-200. 2008
    ..Our data extend the information available on prototypical nAChR antagonists, and establish the alpha4/6 chimera as a useful new tool for screening drugs as selective nAChR antagonists...
  74. pmc Vesicular monoamine transporter 2: role as a novel target for drug development
    Guangrong Zheng
    College of Pharmacy, University of Kentucky, Department of Pharmaceutical Sciences, Lexington, KY 40536 0082, USA
    AAPS J 8:E682-92. 2006
    ..The molecular structure of VMAT2 and its relevance to ligand binding are briefly discussed...
  75. pmc Molecular modeling of mono- and bis-quaternary ammonium salts as ligands at the alpha4beta2 nicotinic acetylcholine receptor subtype using nonlinear techniques
    Joshua T Ayers
    College of Pharmacy, University of Kentucky, Lexington, KY 40536 0082, USA
    AAPS J 7:E678-85. 2005
    ..These QSAR approaches may be a useful to screen and select in silico new drug candidates from larger compound libraries to be further evaluated in in vitro biological assays...
  76. pmc A general procedure for the enantioselective synthesis of the minor tobacco alkaloids nornicotine, anabasine, and anatabine
    Joshua T Ayers
    Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY, USA
    AAPS J 7:E752-8. 2005
    ..Using this approach, the R-(+)- and S-(-)-enantiomers of the above minor tobacco alkaloids were obtained in good overall chemical yield and excellent enantomeric excess...
  77. ncbi request reprint N, N -disubstituted piperazines and homopiperazines: synthesis and affinities at alpha4beta2* and alpha7* neuronal nicotinic acetylcholine receptors
    Jianhong Chen
    Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 725 Rose Street, Lexington, KY 40536 0082, USA
    J Enzyme Inhib Med Chem 21:667-80. 2006
    ..0 microM), and 8-24 (K(i) = 12.8 microM). Thus, linking together a pyridine pi-system and a cyclic amine moiety via a homopiperazine ring affords compounds with low affinity but with good selectivity for alpha4beta2* nAChRs...
  78. pmc Indirect trapping of the retroconjugate addition reaction intermediate involved in the epimerization of lobeline: application to the synthesis of (-)-sedamine
    Guangrong Zheng
    College of Pharmacy, University of Kentucky, Lexington, Kentucky 40536 0082, USA
    J Org Chem 69:8514-7. 2004
    ..This strategy was applied to the conversion of (-)-lobeline to (-)-sedamine in high overall yield...

Research Grants18

  1. Development of Novel Therapies or Methamphetamine Abuse
    Linda Dwoskin; Fiscal Year: 2009
    ..abstract_text> ..
  2. Development of Novel Therapies or Methamphetamine Abuse
    Linda Dwoskin; Fiscal Year: 2007
    ..abstract_text> ..
  3. Developmemt of Novel Treatments for Nicotine Addiction
    Linda Dwoskin; Fiscal Year: 2007
    ..abstract_text> ..
  4. Nicotinic Receptor Regulation of Dopamine Transporter
    Linda Dwoskin; Fiscal Year: 2006
    ..Thus, insight will be provided with respect to the effect of NIC on DA neurotransmission in brain regions associated with drug abuse. ..
  5. DEVELOPMENT OF NOVEL THERAPIES FOR METHAMPHETAMINE ABUSE
    Linda Dwoskin; Fiscal Year: 2003
    ..Thus, these studies will pioneer the development of a novel class of therapeutic agents which target VMAT2 and have potential as efficacious treatments for METH abuse. ..
  6. DEVELOPMENT OF SELECTIVE NICOTINIC RECEPTOR ANTAGONISTS
    Linda Dwoskin; Fiscal Year: 2003
    ..abstract_text> ..
  7. DEVELOPMENT OF SELECTIVE NICOTINIC RECEPTOR ANTAGONISTS
    Linda Dwoskin; Fiscal Year: 2001
    ..These subtype selective nicotinic receptor antagonists would be invaluable neuropharmacological agents for basic and clinical research. ..
  8. Development of Novel Therapies or Methamphetamine Abuse
    Linda Dwoskin; Fiscal Year: 2009
    ....