2022
Pharmacological characterization of 5-iodo-A-85380, a β2-selective nicotinic receptor agonist, in mice
Akinola LS, Bagdas D, Alkhlaif Y, Jackson A, Gurdap CO, Rahimpour E, Carroll FI, Papke RL, Damaj MI. Pharmacological characterization of 5-iodo-A-85380, a β2-selective nicotinic receptor agonist, in mice. Journal Of Psychopharmacology 2022, 36: 1280-1293. PMID: 36321267, PMCID: PMC9817006, DOI: 10.1177/02698811221132214.Peer-Reviewed Original ResearchConceptsNicotinic receptor agonistsReceptor agonistNicotinic acetylcholine receptorsLow sensitivityPharmacological characterizationΑ4β2 receptorsNicotine dependenceNicotinic subunitsPlace preferenceΑ4β2 nAChRsAcetylcholine receptorsPartial agonistFull agonistAgonistsDifferential efficacyBehavioral effectsNeurodegenerative diseasesSubtypesPathological conditionsNAChRsPotential targetPotential roleHypothermiaReceptorsΑ6
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 ResearchConceptsNicotinic 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 desensitizationInflammationAgonistsChapter 33 Targeting Nicotinic Acetylcholine Receptors for the Treatment of Pain
Bagdas D, Kyte S, Toma W, Gurun M, Damaj M. Chapter 33 Targeting Nicotinic Acetylcholine Receptors for the Treatment of Pain. 2019, 259-266. DOI: 10.1016/b978-0-12-813035-3.00033-2.Peer-Reviewed Original ResearchNicotinic acetylcholine receptorsAcetylcholine receptorsNAChR ligandsTreatment of painRecent animal studiesNarrow therapeutic windowPeripheral nervous systemPositive allosteric modulatorsAnalgesic efficacyPain managementChronic painNeuropathic conditionsImmune cellsNovel analgesicsTherapeutic windowAnimal modelsAnimal studiesHuman studiesNervous systemNicotinic agentsAllosteric modulatorsTherapeutic potentialPainPromising agentSilent agonist
2018
Blockade of nicotinic acetylcholine receptor enhances the responsiveness to bupropion in the mouse forced swim test
Bagdas D, AlSharari S, Roni M, Campbell V, Muldoon P, Carroll F, Damaj M. Blockade of nicotinic acetylcholine receptor enhances the responsiveness to bupropion in the mouse forced swim test. Behavioural Brain Research 2018, 360: 262-269. PMID: 30552947, PMCID: PMC6324988, DOI: 10.1016/j.bbr.2018.12.027.Peer-Reviewed Original ResearchConceptsAntidepressant-like effectsImmobility timeWT miceDecreased immobility timeDihydro-β-erythroidineAdult male miceWild-type miceEffects of β2Nicotinic acetylcholine receptorsBaseline immobilityAntidepressant effectsPresent studyJ miceKO miceSwim testMale miceWT littermatesRole of α4Bupropion administrationBupropionAcute dosesFST behaviorTransgenic miceAcetylcholine receptorsNAChR subunitsThe 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 ResearchConceptsAntinociceptive 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 agonistNew Insights on Neuronal Nicotinic Acetylcholine Receptors as Targets for Pain and Inflammation: A Focus on α7 nAChRs
Bagdas D, Gurun M, Flood P, Papke R, Damaj M. New Insights on Neuronal Nicotinic Acetylcholine Receptors as Targets for Pain and Inflammation: A Focus on α7 nAChRs. Current Neuropharmacology 2018, 16: 415-425. PMID: 28820052, PMCID: PMC6018191, DOI: 10.2174/1570159x15666170818102108.Peer-Reviewed Original ResearchConceptsNicotinic acetylcholine receptorsΑ7 nAChRsAcetylcholine receptorsNeuronal nicotinic acetylcholine receptorsPerspective of painChronic pain conditionsTreatment of painRecent animal studiesPain controlPain conditionsSide effectsAnimal studiesTherapeutic targetingPainReceptor typesNAChRsReceptorsInflammationSelective ligandsΑ7Latest findingsTreatmentRecent insightsReviewNicotineCurcumin 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 ResearchConceptsEffect 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
Allosteric modulation of α4β2* nicotinic acetylcholine receptors: Desformylflustrabromine potentiates antiallodynic response of nicotine in a mouse model of neuropathic pain
Bagdas D, Ergun D, Jackson A, Toma W, Schulte M, Damaj M. Allosteric modulation of α4β2* nicotinic acetylcholine receptors: Desformylflustrabromine potentiates antiallodynic response of nicotine in a mouse model of neuropathic pain. European Journal Of Pain 2017, 22: 84-93. PMID: 28809075, PMCID: PMC9829446, DOI: 10.1002/ejp.1092.Peer-Reviewed Original ResearchConceptsPositive allosteric modulatorsChronic neuropathic painNeuropathic painΑ4β2 nAChRsNicotinic acetylcholine receptorsAllosteric modulationAcetylcholine receptorsAntagonist dihydro-β-erythroidineNeuronal nicotinic acetylcholine receptorsChronic constriction injuryEndogenous cholinergic toneNicotine-evoked responsesAnimal pain modelsNicotine-induced antinociceptionDihydro-β-erythroidineMediation of painAlternative treatment strategiesBehavior doseConstriction injuryAntiallodynic effectPain modelPain modulationCholinergic tonePain behaviorAntinociceptive propertiesThe 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 ResearchIn 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 ResearchConceptsΑ7 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 colitis
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 ResearchConceptsPositive 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 edemaSex Differences and Drug Dose Influence the Role of the α-7 Nicotinic Acetylcholine Receptor in the Mouse Dextran Sodium Sulfate-Induced Colitis Model
AlSharari S, Bagdas D, Akbarali H, Cabral G, Carroll I, Damaj I, Lichtman P. Sex Differences and Drug Dose Influence the Role of the α-7 Nicotinic Acetylcholine Receptor in the Mouse Dextran Sodium Sulfate-Induced Colitis Model. The American Journal Of Gastroenterology 2015, 110: s776. DOI: 10.14309/00000434-201510001-01826.Peer-Reviewed Original ResearchNicotinic acetylcholine receptorsColitis modelAcetylcholine receptorsSex differencesDose influenceReceptorsEffects of GAT107, an Allosteric Agonist and Positive Modulator of α7 Nicotinic Acetylcholine Receptors, on Chronic Inflammatory and Neuropathic Pain in Mice
Bagdas D, Wilkerson J, Lichtman A, Thakur G, Damaj M. Effects of GAT107, an Allosteric Agonist and Positive Modulator of α7 Nicotinic Acetylcholine Receptors, on Chronic Inflammatory and Neuropathic Pain in Mice. The FASEB Journal 2015, 29 DOI: 10.1096/fasebj.29.1_supplement.616.12.Peer-Reviewed Original ResearchPositive allosteric modulatorsΑ7 nicotinic acetylcholine receptorNeuropathic painNicotinic acetylcholine receptorsAntinociceptive effectAgo-PAMChronic constriction injury-induced neuropathic painAcetylcholine receptorsAllosteric agonistInjury-induced neuropathic painPain-induced aversionAcetic acid injectionNew pharmacological approachesPlace aversion (CPA) testNovel therapeutic approachesAcute thermal stimulusMassey Cancer CenterComplete Freud'sInflammatory painChronic inflammatoryFormalin testPain modulationPain behaviorCancer CenterSystemic administration
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 ResearchConceptsPositive 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