2021
(E)-3-furan-2-yl-N-phenylacrylamide (PAM-4) decreases nociception and emotional manifestations of neuropathic pain in mice by α7 nicotinic acetylcholine receptor potentiation
Bagdas D, Sevdar G, Gul Z, Younis R, Cavun S, Tae HS, Ortells MO, Arias HR, Gurun MS. (E)-3-furan-2-yl-N-phenylacrylamide (PAM-4) decreases nociception and emotional manifestations of neuropathic pain in mice by α7 nicotinic acetylcholine receptor potentiation. Neurological Research 2021, 43: 1056-1068. PMID: 34281483, DOI: 10.1080/01616412.2021.1949684.Peer-Reviewed Original ResearchMeSH KeywordsAcrylamidesAlpha7 Nicotinic Acetylcholine ReceptorAnalgesicsAnimalsAnxietyBehavior, AnimalDepressionMaleMiceMice, Inbred BALB CNeuralgiaNociceptionConceptsPositive allosteric modulationΑ7 nAChRsNeuropathic painΑ7-selective antagonist methyllycaconitineΑ7 nicotinic acetylcholine receptorChronic constriction injuryPaw licking behaviorNeuropathic pain modelAcute systemic administrationChronic painful conditionsAntidepressant-like activityAnti-nociceptive activityDepression-like behaviorAnxiogenic-like effectsNicotinic acetylcholine receptorsAffective behaviorHuman α7 nAChRConstriction injuryMechanical allodyniaFormalin testPain modelAntagonist methyllycaconitineChronic painPainful conditionsRat α7 nAChR
2020
Impact of menthol on nicotine intake and preference in mice: Concentration, sex, and age differences
Bagdas D, Jackson A, Carper M, Chen RY, Akinola LS, Damaj MI. Impact of menthol on nicotine intake and preference in mice: Concentration, sex, and age differences. Neuropharmacology 2020, 179: 108274. PMID: 32827516, PMCID: PMC7572603, DOI: 10.1016/j.neuropharm.2020.108274.Peer-Reviewed Original ResearchConceptsOral nicotine consumptionEffect of mentholImpact of mentholNicotine consumptionFemale miceNicotine intakeΑ7 nicotinic acetylcholine receptorMenthol concentrationNicotine solutionHigher nicotine intakeAdolescent female miceMale C57BL/6J miceTwo-bottle choice paradigmWild-type miceNicotinic acetylcholine receptorsConcentration-dependent mannerOral nicotineC57BL/6J miceKO miceMale miceType miceMouse modelAcetylcholine receptorsHigh menthol concentrationAdult counterparts
2019
A silent agonist of α7 nicotinic acetylcholine receptors modulates inflammation ex vivo and attenuates EAE
Godin J, Roy P, Quadri M, Bagdas D, Toma W, Narendrula-Kotha R, Kishta O, Damaj M, Horenstein N, Papke R, Simard A. A silent agonist of α7 nicotinic acetylcholine receptors modulates inflammation ex vivo and attenuates EAE. Brain Behavior And Immunity 2019, 87: 286-300. PMID: 31874200, PMCID: PMC7604877, DOI: 10.1016/j.bbi.2019.12.014.Peer-Reviewed Original ResearchMeSH KeywordsAlpha7 Nicotinic Acetylcholine ReceptorAnimalsEncephalomyelitis, Autoimmune, ExperimentalInflammationMiceNicotinic AgonistsReceptors, NicotinicConceptsNicotinic acetylcholine receptorsSilent agonistInflammatory painCytokine productionΑ7 nAChRsAnimal modelsAcetylcholine receptorsΑ7 nicotinic acetylcholine receptorNon-neuronal nAChRsExperimental autoimmune encephalomyelitisChronic inflammatory painAnti-inflammatory compoundsInflammation ex vivoChannel openingAutoimmune encephalomyelitisAntagonist mecamylamineMultiple sclerosisInflammatory disordersModulates inflammationMacrophage numbersDisease manifestationsNervous systemReceptor desensitizationInflammationAgonistsThe α7 nicotinic receptor silent agonist R-47 prevents and reverses paclitaxel-induced peripheral neuropathy in mice without tolerance or altering nicotine reward and withdrawal
Toma W, Kyte SL, Bagdas D, Jackson A, Meade JA, Rahman F, Chen ZJ, Del Fabbro E, Cantwell L, Kulkarni A, Thakur GA, Papke RL, Bigbee JW, Gewirtz DA, Damaj MI. The α7 nicotinic receptor silent agonist R-47 prevents and reverses paclitaxel-induced peripheral neuropathy in mice without tolerance or altering nicotine reward and withdrawal. Experimental Neurology 2019, 320: 113010. PMID: 31299179, PMCID: PMC6708482, DOI: 10.1016/j.expneurol.2019.113010.Peer-Reviewed Original ResearchConceptsChemotherapy-induced peripheral neuropathyPeripheral neuropathyNicotine rewardPaclitaxel treatmentRewarding effectsTreatment of CIPNPaclitaxel-induced mechanical hypersensitivityTumor-bearing NSG micePaclitaxel-induced peripheral neuropathyNon-small cell lung cancer cell linesCell lung cancer cell linesA549 non-small cell lung cancer cell lineMecamylamine-precipitated withdrawalAntitumor activityIntraepidermal nerve fibersLung cancer cell linesLung tumor growthNSCLC cell viabilityTumor-bearing miceIntrinsic rewarding effectsPlace preference testCancer cell linesConditioned place preference testMechanical hypersensitivityAgonist R
2018
The antinociceptive and anti-inflammatory properties of the α7 nAChR weak partial agonist p-CF3 N,N-diethyl-N’-phenylpiperazine
Quadri M, Bagdas D, Toma W, Stokes C, Horenstein N, Damaj M, Papke R. The antinociceptive and anti-inflammatory properties of the α7 nAChR weak partial agonist p-CF3 N,N-diethyl-N’-phenylpiperazine. Journal Of Pharmacology And Experimental Therapeutics 2018, 367: jpet.118.249904. PMID: 30111636, PMCID: PMC7593094, DOI: 10.1124/jpet.118.249904.Peer-Reviewed Original ResearchMeSH KeywordsAcetylcholineAllosteric RegulationAlpha7 Nicotinic Acetylcholine ReceptorAnalgesicsAnimalsAnti-Inflammatory AgentsHumansNaphthalenesNicotinic AgonistsPiperazinesQuinolinesSulfonamidesXenopus laevisConceptsAntinociceptive activitySelective antagonist methyllycaconitineAnti-inflammatory therapyAnti-inflammatory componentsAnti-inflammatory propertiesPositive allosteric modulatorsNon-neuronal cellsNicotinic acetylcholine receptorsVivo antinociceptive activityAntiedema effectInflammatory painAntagonist methyllycaconitineChronic painInflammatory diseasesHeteromeric nAChRsReceptor subtypesElectrophysiological profileNoncompetitive antagonistAcetylcholine receptorsAgonist activityPartial agonistAllosteric modulatorsSuch drugsPromising drug targetSilent agonistCurcumin acts as a positive allosteric modulator of α7-nicotinic acetylcholine receptors and reverses nociception in mouse models of inflammatory pain
El Nebrisi E, Bagdas D, Toma W, Al Samri H, Brodzik A, Alkhlaif Y, Yang K, Howarth F, Damaj I, Oz M. Curcumin acts as a positive allosteric modulator of α7-nicotinic acetylcholine receptors and reverses nociception in mouse models of inflammatory pain. Journal Of Pharmacology And Experimental Therapeutics 2018, 365: jpet.117.245068. PMID: 29339457, PMCID: PMC7947331, DOI: 10.1124/jpet.117.245068.Peer-Reviewed Original ResearchMeSH KeywordsAllosteric RegulationAlpha7 Nicotinic Acetylcholine ReceptorAnimalsBenzamidesBridged Bicyclo CompoundsCurcuminDisease Models, AnimalFemaleInflammationMaleMiceMotor ActivityNociceptionPainConceptsEffect of curcuminPositive allosteric modulatorsMouse modelVisceral painAntinociceptive effectNACh receptorsAcetylcholine receptorsAllosteric modulatorsΑ7 nicotinic acetylcholine receptorVisceral pain modelHuman nicotinic acetylcholine receptorNicotinic acetylcholine receptorsInflammatory painPain modelNociceptive behaviorReceptor agonistSignificant potentiationDependent ClLocomotor activityACh concentrationPainNociceptionReceptorsTonicG proteins
2017
The interaction between alpha 7 nicotinic acetylcholine receptor and nuclear peroxisome proliferator-activated receptor-α represents a new antinociceptive signaling pathway in mice
Donvito G, Bagdas D, Toma W, Rahimpour E, Jackson A, Meade JA, AlSharari S, Kulkarni AR, Carroll F, Lichtman AH, Papke RL, Thakur GA, Damaj M. The interaction between alpha 7 nicotinic acetylcholine receptor and nuclear peroxisome proliferator-activated receptor-α represents a new antinociceptive signaling pathway in mice. Experimental Neurology 2017, 295: 194-201. PMID: 28606623, PMCID: PMC5558428, DOI: 10.1016/j.expneurol.2017.06.014.Peer-Reviewed Original ResearchMeSH KeywordsAlpha7 Nicotinic Acetylcholine ReceptorAmidesAnimalsAzabicyclo CompoundsBenzamidesBridged Bicyclo CompoundsCannabinoid Receptor AntagonistsEthanolaminesFuransMaleMiceMice, Inbred ICRNicotinic AntagonistsNociceptionOxazolesPain MeasurementPalmitic AcidsPPAR alphaReceptor Cross-TalkSignal TransductionTyrosineConceptsPositive allosteric modulatorsAntinociceptive effectNicotinic acetylcholine receptorsΑ7 nAChRsAlpha 7 nicotinic acetylcholine receptorAcetylcholine receptorsNuclear peroxisome proliferator-activated receptorsΑ7 nicotinic acetylcholine receptorPeroxisome proliferator-activated receptorAnalgesic drug developmentProliferator-activated receptorAttenuated formalinAntinociceptive responseFormalin testΑ7 agonistsAntagonist SR144528Nociceptive behaviorTonic painBrain levelsAntagonist GW6471Exogenous administrationΑ7 nicotinicMouse modelCannabinoid CBOrthosteric agonistsPersistent activation of α7 nicotinic ACh receptors associated with stable induction of different desensitized states
Papke R, Stokes C, Damaj M, Thakur G, Manther K, Treinin M, Bagdas D, Kulkarni A, Horenstein N. Persistent activation of α7 nicotinic ACh receptors associated with stable induction of different desensitized states. British Journal Of Pharmacology 2017, 175: 1838-1854. PMID: 28477386, PMCID: PMC5979752, DOI: 10.1111/bph.13851.Peer-Reviewed Original ResearchMeSH KeywordsAllosteric RegulationAlpha7 Nicotinic Acetylcholine ReceptorAnimalsAzabicyclo CompoundsFemaleFuransQuinolinesSulfonamidesXenopus laevisIn vivo interactions between α7 nicotinic acetylcholine receptor and nuclear peroxisome proliferator-activated receptor-α: Implication for nicotine dependence
Jackson A, Bagdas D, Muldoon PP, Lichtman AH, Carroll FI, Greenwald M, Miles MF, Damaj MI. In vivo interactions between α7 nicotinic acetylcholine receptor and nuclear peroxisome proliferator-activated receptor-α: Implication for nicotine dependence. Neuropharmacology 2017, 118: 38-45. PMID: 28279662, PMCID: PMC5410388, DOI: 10.1016/j.neuropharm.2017.03.005.Peer-Reviewed Original ResearchMeSH KeywordsAlpha7 Nicotinic Acetylcholine ReceptorAnesthetics, LocalAnimalsBenzamidesBridged Bicyclo CompoundsCocaineConditioning, OperantDisease Models, AnimalFenofibrateHypolipidemic AgentsMaleMiceMice, Inbred ICRNicotineNicotinic AgonistsOxazolesPPAR alphaPyrimidinesSelf AdministrationSubstance Withdrawal SyndromeTobacco Use DisorderTyrosineConceptsNicotine dependenceNicotinic acetylcholine receptorsNicotine rewardΑ7 nAChRsNicotine CPPWY-14643Acetylcholine receptorsRewarding propertiesNuclear peroxisome proliferator-activated receptorsΑ7 nicotinic acetylcholine receptorVentral tegmental area dopamine cellsEffect of α7Peroxisome proliferator-activated receptorNicotine withdrawal signsSmoking cessation therapyChronic tobacco useCurrent smoking cessation therapiesPPARα antagonist GW6471Main addictive componentPPARα-dependent mannerProliferator-activated receptorNicotine rewarding propertiesPlace preference testHomomeric α7 nAChRsSelf-administration model
2016
Sex Differences and Drug Dose Influence the Role of the α7 Nicotinic Acetylcholine Receptor in the Mouse Dextran Sodium Sulfate-Induced Colitis Model
AlSharari S, Bagdas D, Akbarali H, Lichtman P, Raborn E, Cabral G, Carroll F, McGee E, Damaj M. Sex Differences and Drug Dose Influence the Role of the α7 Nicotinic Acetylcholine Receptor in the Mouse Dextran Sodium Sulfate-Induced Colitis Model. Nicotine & Tobacco Research 2016, 19: 460-468. PMID: 27639096, PMCID: PMC6894014, DOI: 10.1093/ntr/ntw245.Peer-Reviewed Original ResearchMeSH KeywordsAlpha7 Nicotinic Acetylcholine ReceptorAnimalsAnti-Inflammatory AgentsBridged Bicyclo Compounds, HeterocyclicColitisDextran SulfateDisease Models, AnimalFemaleInflammationIsoxazolesMaleMiceMice, KnockoutPhenylurea CompoundsQuinuclidinesConceptsΑ7 nicotinic acetylcholine receptorWild-type miceColitis severityNicotinic acetylcholine receptorsFemale miceHigher tumor necrosis factor-alpha levelsAcetylcholine receptorsTumor necrosis factor-alpha levelsNecrosis factor-alpha levelsLittermate wild-type miceAnti-colitis activityAnti-colitis effectΑ7 knockout miceDextran sodium sulfatePathogenesis of colitisAnti-inflammatory effectsFemale adult miceViable therapeutic approachSeverity of diseaseSex differencesColon lengthDisease activityColonic levelsColitis modelUlcerative colitisThe α7 nicotinic receptor dual allosteric agonist and positive allosteric modulator GAT107 reverses nociception in mouse models of inflammatory and neuropathic pain
Bagdas D, Wilkerson J, Kulkarni A, Toma W, AlSharari S, Gul Z, Lichtman A, Papke R, Thakur G, Damaj M. The α7 nicotinic receptor dual allosteric agonist and positive allosteric modulator GAT107 reverses nociception in mouse models of inflammatory and neuropathic pain. British Journal Of Pharmacology 2016, 173: 2506-2520. PMID: 27243753, PMCID: PMC4959951, DOI: 10.1111/bph.13528.Peer-Reviewed Original ResearchMeSH KeywordsAllosteric RegulationAlpha7 Nicotinic Acetylcholine ReceptorAnimalsDisease Models, AnimalDose-Response Relationship, DrugInflammationMaleMiceMice, Inbred C57BLMice, Inbred ICRNeuralgiaQuinolinesStructure-Activity RelationshipSulfonamidesConceptsPositive allosteric modulatorsNeuropathic painPain modelAntinociceptive effectSpinal cordTail flickChronic constriction injury (CCI) neuropathic pain modelAllosteric agonistDose-dependent antinociceptive effectΑ7 nicotinic ACh receptorsGlial fibrillary acidic proteinNeuropathic pain modelAstrocyte-specific glial fibrillary acidic proteinInflammatory pain modelAcetic acid injectionHot-plate assayEffective pharmacological strategiesNicotinic ACh receptorsNovel therapeutic approachesFibrillary acidic proteinDorsal hornFormalin testPain modulationSubchronic administrationLocus of action
2015
The Antinociceptive and Antiinflammatory Properties of 3-furan-2-yl-N-p-tolyl-acrylamide, a Positive Allosteric Modulator of &agr;7 Nicotinic Acetylcholine Receptors in Mice
Bagdas D, Targowska-Duda K, López J, Perez E, Arias H, Damaj M. The Antinociceptive and Antiinflammatory Properties of 3-furan-2-yl-N-p-tolyl-acrylamide, a Positive Allosteric Modulator of &agr;7 Nicotinic Acetylcholine Receptors in Mice. Anesthesia & Analgesia 2015, 121: 1369-1377. PMID: 26280585, PMCID: PMC4847442, DOI: 10.1213/ane.0000000000000902.Peer-Reviewed Original ResearchMeSH KeywordsAcrylamidesAllosteric RegulationAlpha7 Nicotinic Acetylcholine ReceptorAnalgesicsAnimalsAnti-Inflammatory AgentsFuransMaleMiceMice, Inbred ICRPainConceptsPositive allosteric modulatorsType II positive allosteric modulatorsNeuropathic pain modelInflammatory painNicotinic acetylcholine receptorsNeuropathic painPain modelCarrageenan testAntiinflammatory propertiesChronic constriction injury-induced neuropathic painAcetylcholine receptorsInjury-induced neuropathic painAllosteric modulatorsΑ7 nicotinic acetylcholine receptorSelective α7 agonistPlace aversion (CPA) testExperience of painEfficacy of agonistsEndogenous neurotransmissionMechanical allodyniaThermal hyperalgesiaTime-dependent mannerAntinociceptive effectComplete Freund'sPaw edema
2014
The analgesic-like properties of the alpha7 nAChR silent agonist NS6740 is associated with non-conducting conformations of the receptor
Papke R, Bagdas D, Kulkarni A, Gould T, AlSharari S, Thakur G, Damaj M. The analgesic-like properties of the alpha7 nAChR silent agonist NS6740 is associated with non-conducting conformations of the receptor. Neuropharmacology 2014, 91: 34-42. PMID: 25497451, PMCID: PMC4312719, DOI: 10.1016/j.neuropharm.2014.12.002.Peer-Reviewed Original ResearchMeSH KeywordsAlpha7 Nicotinic Acetylcholine ReceptorAnalgesics, Non-NarcoticAnimalsAzabicyclo CompoundsFuransHumansMaleMice, Inbred ICRNeuralgiaPain ThresholdProtein ConformationProtein SubunitsXenopusConceptsPositive allosteric modulatorsChronic painAntinociceptive activityΑ7 nicotinic acetylcholine receptorAnalgesic-like propertiesPain-induced aversionNerve injury modelAcute thermal painNon-neuronal cellsNicotinic acetylcholine receptorsImportant affective componentIon channelsNeuropathic painPain modelNociceptive behaviorInflammatory diseasesInjury modelNS6740Α7 nAChRsΑ7 receptorsThermal painPainAcetylcholine receptorsChannel activatorNeurological disorders
2011
The antihyperalgesic effect of cytidine-5′-diphosphate-choline in neuropathic and inflammatory pain models
Bagdas D, Sonat F, Hamurtekin E, Sonal S, Gurun M. The antihyperalgesic effect of cytidine-5′-diphosphate-choline in neuropathic and inflammatory pain models. Behavioural Pharmacology 2011, 22: 589-598. PMID: 21836465, DOI: 10.1097/fbp.0b013e32834a1efb.Peer-Reviewed Original ResearchConceptsNeuropathic pain modelAntihyperalgesic effectPain modelChronic constriction injury-induced neuropathic pain modelNonselective muscarinic receptor antagonist atropineNonselective opioid receptor antagonist naloxoneΓ-aminobutyric acid B receptorsNicotinic ACh receptor antagonistsReceptor antagonist CGP 35348Muscarinic receptor antagonist atropineNicotinic receptor antagonist mecamylamineOpioid receptor antagonist naloxoneCholine uptake inhibitor hemicholinium-3CDP-cholineEffect of intracerebroventricularlyAntagonist CGP 35348Central opioid receptorsInflammatory pain modelACh receptor antagonistNicotinic ACh receptorsCGP 35348Mechanical hyperalgesiaNeuropathic painAntagonist atropineAntagonist naloxone