2005
Synthesis, Radiosynthesis, and Biological Evaluation of Carbon-11 and Fluorine-18 (N-Fluoroalkyl) Labeled 2β-Carbomethoxy-3β-(4'-(3-furyl)phenyl)tropanes and -nortropanes: Candidate Radioligands for in Vivo Imaging of the Serotonin Transporter with Positron Emission Tomography
Stehouwer J, Plisson C, Jarkas N, Zeng F, Voll R, Williams L, Martarello L, Votaw J, Tamagnan G, Goodman M. Synthesis, Radiosynthesis, and Biological Evaluation of Carbon-11 and Fluorine-18 (N-Fluoroalkyl) Labeled 2β-Carbomethoxy-3β-(4'-(3-furyl)phenyl)tropanes and -nortropanes: Candidate Radioligands for in Vivo Imaging of the Serotonin Transporter with Positron Emission Tomography. Journal Of Medicinal Chemistry 2005, 48: 7080-7083. PMID: 16250668, DOI: 10.1021/jm0504095.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBinding, CompetitiveBrainCarbon RadioisotopesCell LineDopamine Plasma Membrane Transport ProteinsFluorine RadioisotopesFuransHumansLigandsMacaca fascicularisMacaca mulattaNorepinephrine Plasma Membrane Transport ProteinsNortropanesPositron-Emission TomographyRadioligand AssayRadiopharmaceuticalsSerotonin Plasma Membrane Transport ProteinsStructure-Activity RelationshipTropanesA Close Structural Analog of 2-Methyl-6-(phenylethynyl)-pyridine Acts as a Neutral Allosteric Site Ligand on Metabotropic Glutamate Receptor Subtype 5 and Blocks the Effects of Multiple Allosteric Modulators
Rodriguez A, Nong Y, Sekaran N, Alagille D, Tamagnan G, Conn P. A Close Structural Analog of 2-Methyl-6-(phenylethynyl)-pyridine Acts as a Neutral Allosteric Site Ligand on Metabotropic Glutamate Receptor Subtype 5 and Blocks the Effects of Multiple Allosteric Modulators. Molecular Pharmacology 2005, 68: 1793-1802. PMID: 16155210, DOI: 10.1124/mol.105.016139.Peer-Reviewed Original ResearchConceptsMetabotropic glutamate receptor subtype 5Subtype 5Allosteric siteG protein-coupled receptorsProtein-coupled receptorsMajor excitatory neurotransmitterCentral nervous systemMPEP siteAntagonist MPEPBinding of glutamateOnly partial inhibitionExcitatory neurotransmitterSubthalamic nucleusCalcium mobilizationNervous systemSite ligandsAllosteric modulatorsPartial antagonistValuable new toolNovel compoundsValuable new insightsOrthosteric ligandsAllosteric modulationFunctional effectsNative systemsFunctionalization at position 3 of the phenyl ring of the potent mGluR5 noncompetitive antagonists MPEP
Alagille D, Baldwin R, Roth B, Wroblewski J, Grajkowska E, Tamagnan G. Functionalization at position 3 of the phenyl ring of the potent mGluR5 noncompetitive antagonists MPEP. Bioorganic & Medicinal Chemistry Letters 2005, 15: 945-949. PMID: 15686891, DOI: 10.1016/j.bmcl.2004.12.047.Peer-Reviewed Original ResearchSynthesis and receptor assay of aromatic–ethynyl–aromatic derivatives with potent mGluR5 antagonist activity
Alagille D, Baldwin R, Roth B, Wroblewski J, Grajkowska E, Tamagnan G. Synthesis and receptor assay of aromatic–ethynyl–aromatic derivatives with potent mGluR5 antagonist activity. Bioorganic & Medicinal Chemistry 2005, 13: 197-209. PMID: 15582465, DOI: 10.1016/j.bmc.2004.09.042.Peer-Reviewed Original ResearchConceptsNoncompetitive antagonistMetabotropic glutamate receptor subtype 5Potent mGluR5 antagonistNervous system disordersMGluR5 antagonistSubtype 5Novel noncompetitive antagonistSystem disordersAntagonist activityAntagonistPotential therapeuticsDrug addictionSAR studiesInactive productsCritical roleMGluR5MPEPPain
2004
Synthesis and monoamine transporter affinity of 3′-analogs of 2-β-carbomethoxy-3-β-(4′-iodophenyl)tropane (β-CIT)
Bois F, Baldwin R, Kula N, Baldessarini R, Innis R, Tamagnan G. Synthesis and monoamine transporter affinity of 3′-analogs of 2-β-carbomethoxy-3-β-(4′-iodophenyl)tropane (β-CIT). Bioorganic & Medicinal Chemistry Letters 2004, 14: 2117-2120. PMID: 15080991, DOI: 10.1016/j.bmcl.2004.02.043.Peer-Reviewed Original ResearchRadiosynthesis of [18F] N-(3-Fluoropropyl)-2-β-Carbomethoxy-3-β-(4-Bromophenyl) Nortropane and the regional brain uptake in non human primate using PET
Chaly T, Baldwin R, Neumeyer J, Hellman M, Dhawan V, Garg P, Tamagnan G, Staley J, Al-Tikriti M, Hou Y, Zoghbi S, Gu X, Zong R, Eidelberg D. Radiosynthesis of [18F] N-(3-Fluoropropyl)-2-β-Carbomethoxy-3-β-(4-Bromophenyl) Nortropane and the regional brain uptake in non human primate using PET. Nuclear Medicine And Biology 2004, 31: 125-131. PMID: 14741577, DOI: 10.1016/s0969-8051(03)00110-0.Peer-Reviewed Original ResearchConceptsBrain uptakeDopamine transporterRegional brain uptakeGood brain uptakeNon-target ratioDAT imagingPlasma metabolite analysisTarget ratioΒ-carbomethoxyHigh uptakeImaging agentVivo propertiesHuman primatesRadiochemical purityHigh targetUptakeParent compoundStriatumMetabolite analysisRadiosynthesis
2003
Influence of acetylcholine levels on the binding of a SPECT nicotinic acetylcholine receptor ligand [123I]5‐I‐A‐85380
Fujita M, Al‐Tikriti M, Tamagnan G, Zoghbi S, Bozkurt A, Baldwin R, Innis R. Influence of acetylcholine levels on the binding of a SPECT nicotinic acetylcholine receptor ligand [123I]5‐I‐A‐85380. Synapse 2003, 48: 116-122. PMID: 12645036, DOI: 10.1002/syn.10194.Peer-Reviewed Original ResearchConceptsPhysostigmine administrationThalamic activityPlasma levelsAcetylcholine levelsNicotinic ACh receptorsNicotinic acetylcholine receptor ligandsElevated ACh levelsSingle photon emissionAcetylcholine receptor ligandsACh levelsACh receptorsTomography ligandSustained increasePhysostigmineAdministrationReceptor ligandsAcetylcholinesterase inhibitorsPhoton emissionVivoReceptorsLevelsBolusActivityNAChRsStudy
2002
Synthesis, Receptor Potency, and Selectivity of Halogenated Diphenylpiperidines as Serotonin 5-HT2A Ligands for PET or SPECT Brain Imaging
Fu X, Tan P, Kula N, Baldessarini R, Tamagnan G, Innis R, Baldwin R. Synthesis, Receptor Potency, and Selectivity of Halogenated Diphenylpiperidines as Serotonin 5-HT2A Ligands for PET or SPECT Brain Imaging. Journal Of Medicinal Chemistry 2002, 45: 2319-2324. PMID: 12014970, DOI: 10.1021/jm0200411.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCOS CellsHumansIn Vitro TechniquesLigandsPiperidinesProsencephalonRadioligand AssayRatsReceptor, Serotonin, 5-HT2AReceptor, Serotonin, 5-HT2CReceptors, Adrenergic, alpha-1Receptors, Adrenergic, alpha-2Receptors, Dopamine D2Receptors, SerotoninStructure-Activity RelationshipTomography, Emission-ComputedTomography, Emission-Computed, Single-Photon
2001
Synthesis of Cyclopentadienyltricarbonyl Rhenium Phenyltropanes by Double Ligand Transfer: Organometallic Ligands for the Dopamine Transporter
Cesati R, Tamagnan G, Baldwin R, Zoghbi S, Innis R, Kula N, Baldessarini R, Katzenellenbogen J. Synthesis of Cyclopentadienyltricarbonyl Rhenium Phenyltropanes by Double Ligand Transfer: Organometallic Ligands for the Dopamine Transporter. Bioconjugate Chemistry 2001, 13: 29-39. PMID: 11792176, DOI: 10.1021/bc010011x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBinding, CompetitiveChemical PhenomenaChemistry, PhysicalChromatography, Thin LayerDopamine Plasma Membrane Transport ProteinsIndicators and ReagentsKineticsLigandsMagnetic Resonance SpectroscopyMembrane GlycoproteinsMembrane Transport ProteinsMiceNeostriatumNerve Tissue ProteinsOrganometallic CompoundsRheniumSpectrophotometry, UltravioletTropanesConceptsExcellent functional group toleranceLigand transfer reactionDouble ligand transfer reactionDouble-ligand transferFunctional group toleranceOrganometallic ligandsRhenium systemsLigand transferTransfer reactionsGroup toleranceDirect preparationFerrocene precursorsReasonable yieldsReactionConjugatesModular natureFerrocenePerrhenateLigandsCompoundsSynthesisConvenient mannerPrecursorsPreparationBinderMeasurement of plasma metabolites of (S)-5-[123I]iodo-3- (2-azetidinylmethoxy)pyridine (5-IA-85380), a nicotinic acetylcholine receptor imaging agent, in nonhuman primates
Zoghbi S, Tamagnan G, Fujita M, Baldwin R, Al-Tikriti M, Amici L, Seibyl J, Innis R. Measurement of plasma metabolites of (S)-5-[123I]iodo-3- (2-azetidinylmethoxy)pyridine (5-IA-85380), a nicotinic acetylcholine receptor imaging agent, in nonhuman primates. Nuclear Medicine And Biology 2001, 28: 91-96. PMID: 11182569, DOI: 10.1016/s0969-8051(00)00188-8.Peer-Reviewed Original ResearchConceptsReceptor imaging agentNicotinic acetylcholine receptorsPotential SPECT tracerRadioactive bloodTobacco dependencePlasma concentrationsParent compoundPolar radiometaboliteAcetylcholine receptorsPlasma metabolitesProtein-free plasmaRadioactivity accumulationNeurodegenerative diseasesSPECT tracerWhole bloodFree radioiodideImaging agentEqual volumeVivo quantificationRadiometabolitesBloodReceptorsPlasmaThyroidMin
2000
Measurement of alpha4beta2 nicotinic acetylcholine receptors with [123I]5-I-A-85380 SPECT.
Fujita M, Tamagnan G, Zoghbi S, Al-Tikriti M, Baldwin R, Seibyl J, Innis R. Measurement of alpha4beta2 nicotinic acetylcholine receptors with [123I]5-I-A-85380 SPECT. Journal Of Nuclear Medicine 2000, 41: 1552-60. PMID: 10994738.Peer-Reviewed Original ResearchMeSH KeywordsAlkaloidsAnimalsAzetidinesAzocinesBinding, CompetitiveBrainCerebellumImage Processing, Computer-AssistedInfusions, IntravenousInjections, IntravenousIodine RadioisotopesKineticsLeast-Squares AnalysisMagnetic Resonance ImagingPapioQuinolizinesReceptors, NicotinicThalamusTomography, Emission-Computed, Single-PhotonConceptsNicotinic acetylcholine receptorsAlpha4beta2 nAChRsAcetylcholine receptorsNew SPECT tracerAlpha4beta2 nicotinic acetylcholine receptorsPotential therapeutic roleAppropriate outcome measuresTotal distribution volumeTherapeutic roleTobacco dependenceSubcutaneous injectionBolus injectionOutcome measuresIntravenous injectionBaboon brainBolus/Alzheimer's diseaseDistribution volumeNeuropsychiatric disordersSPECT tracerCompartment modelBolus studiesInfusion ratioThalamusBolusSynthesis and monoamine transporter affinity of 2β-carbomethoxy-3β-(2″-, 3″- or 4″-substituted) biphenyltropanes
Tamagnan G, Baldwin R, Kula N, Baldessarini R, Innis R. Synthesis and monoamine transporter affinity of 2β-carbomethoxy-3β-(2″-, 3″- or 4″-substituted) biphenyltropanes. Bioorganic & Medicinal Chemistry Letters 2000, 10: 1783-1785. PMID: 10969967, DOI: 10.1016/s0960-894x(00)00317-6.Peer-Reviewed Original ResearchAnimalsCarrier ProteinsCocaineDopamineDopamine Plasma Membrane Transport ProteinsMembrane GlycoproteinsMembrane Transport ProteinsMolecular StructureNerve Tissue ProteinsNorepinephrineNorepinephrine Plasma Membrane Transport ProteinsProsencephalonRadioligand AssayRatsSerotoninSerotonin Plasma Membrane Transport ProteinsSymportersTropanesSPECT imaging with the D4 receptor antagonist L-750,667 in nonhuman primate brain
Staley J, Tamagnan G, Baldwin R, Fujita M, Tikriti M, Eshima L, Thornback J, Roe D, Lu L, Seibyl J, Innis R. SPECT imaging with the D4 receptor antagonist L-750,667 in nonhuman primate brain. Nuclear Medicine And Biology 2000, 27: 547-556. PMID: 11056368, DOI: 10.1016/s0969-8051(00)00129-3.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBasal GangliaBinding, CompetitiveBrainBrain StemCerebellumDopamine AntagonistsDopamine D2 Receptor AntagonistsFrontal LobeGyrus CinguliImidazolesIodine RadioisotopesOccipital LobeOrgan SpecificityPapioParietal LobePyridinesPyrimidinesPyrrolesReceptors, Dopamine D4Temporal LobeTissue DistributionTomography, Emission-Computed, Single-PhotonConceptsNGD 94D4 receptor antagonist LBrain regionsReceptor antagonist LConstant infusion paradigmNonhuman primate brainSingle photon emissionSaturating dosesAntagonist LBasal gangliaBrain uptakeInfusion paradigmOccipital cortexMin postinjectionSuitable radiotracerPrimate brainCingulate cortexNonhuman primatesTomography imagingReceptor ligandsPhoton emissionBolusCortexBrainReceptorsCyclopentadienyltricarbonylrheniumbenzazepines: synthesis and binding affinity
Tamagnan G, Baldwin R, Kula N, Baldessarini R, Innis R. Cyclopentadienyltricarbonylrheniumbenzazepines: synthesis and binding affinity. Bioorganic & Medicinal Chemistry Letters 2000, 10: 1113-1115. PMID: 10843230, DOI: 10.1016/s0960-894x(00)00185-2.Peer-Reviewed Original Research5-Iodo-A-85380, an α4β2 Subtype-Selective Ligand for Nicotinic Acetylcholine Receptors
Mukhin A, Gündisch D, Horti A, Koren A, Tamagnan G, Kimes A, Chambers J, Vaupel D, King S, Picciotto M, Innis R, London E. 5-Iodo-A-85380, an α4β2 Subtype-Selective Ligand for Nicotinic Acetylcholine Receptors. Molecular Pharmacology 2000, 57: 642-649. PMID: 10692507, DOI: 10.1124/mol.57.3.642.Peer-Reviewed Original ResearchConceptsNicotinic acetylcholine receptorsAlpha4beta2 nAChRsAcetylcholine receptorsNeuronal nicotinic acetylcholine receptorsAffinity of epibatidineRat adrenal glandMuscle-type nAChRsSubtype-selective ligandsAlpha4beta2 subtypeAdrenal glandRat brainSelective radioligandBrain regionsNAChRsBeta4 subunitsRadioiodinated ligandBeta2 subunitVivo studiesEpibatidineVivo experimentsHuman brainSubtypesRadioligandBrainReceptors
1999
Nonisotopic surrogates for technetium as ligands for monoamine transporters.
Tamagnan G, Gao Y, Xu L, Kula N, Baldessarini R, Neumeyer J. Nonisotopic surrogates for technetium as ligands for monoamine transporters. Advances In Neurology 1999, 80: 99-103. PMID: 10410707.Peer-Reviewed Original Research
1996
N-Substituted Analogs of 2β-Carbomethoxy-3β-(4‘-iodophenyl)tropane (β-CIT) with Selective Affinity to Dopamine or Serotonin Transporters in Rat Forebrain
Neumeyer J, Tamagnan G, Wang S, Gao Y, Milius R, Kula N, Baldessarini R. N-Substituted Analogs of 2β-Carbomethoxy-3β-(4‘-iodophenyl)tropane (β-CIT) with Selective Affinity to Dopamine or Serotonin Transporters in Rat Forebrain. Journal Of Medicinal Chemistry 1996, 39: 543-548. PMID: 8558525, DOI: 10.1021/jm9505324.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBinding SitesCarrier ProteinsCocaineDopamineDopamine Plasma Membrane Transport ProteinsMagnetic Resonance SpectroscopyMembrane GlycoproteinsMembrane Transport ProteinsMolecular ProbesNerve Tissue ProteinsProsencephalonRadioligand AssayRatsSerotoninSerotonin Plasma Membrane Transport ProteinsSpectrometry, Mass, Fast Atom BombardmentConceptsBeta-CITN-fluoropropylMood-elevating drugsRat brain tissueBeta-carbomethoxy-3 betaDA neuronsSerotonin neuronsDA transporterNeuropharmacological evaluationRat forebrainBrain tissueImproved markersSerotonin transporterDAT affinityNeuronsDopamineBetaDAT selectivitySelective affinityTransportersHigh affinityEster analoguesSerotoninForebrainNovel series