2019
Chapter 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
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 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 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 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
Reversal of Nicotine Withdrawal Signs Through Positive Allosteric Modulation of α4β2 Nicotinic Acetylcholine Receptors in Male Mice
Hamouda AK, Jackson A, Bagdas D, Damaj M. Reversal of Nicotine Withdrawal Signs Through Positive Allosteric Modulation of α4β2 Nicotinic Acetylcholine Receptors in Male Mice. Nicotine & Tobacco Research 2017, 20: 903-907. PMID: 29059422, PMCID: PMC5991208, DOI: 10.1093/ntr/ntx183.Peer-Reviewed Original ResearchConceptsNicotine withdrawal symptomsSpontaneous nicotine withdrawalNicotine withdrawal signsNicotine withdrawalWithdrawal symptomsPositive allosteric modulatorsCessation aidWithdrawal signsMale miceMouse modelAllosteric modulatorsNicotinic acetylcholine receptor agonistNAChR-positive allosteric modulatorsAcetylcholine receptor agonistDose-dependent reversalICR male miceΑ4β2 nicotinic acetylcholine receptorsPositive allosteric modulationAnxiety-like behaviorNicotinic acetylcholine receptorsPotential clinical useAcute injectionRelapse rateTobacco smokingDay infusionAllosteric 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 Research
2016
The 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 ResearchConceptsPositive 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 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 edemaEffects 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 disordersNicotinic Receptors as Targets for Novel Analgesics and Anti-inflammatory Drugs
Damaj M, Freitas K, Bagdas D, Flood P. Nicotinic Receptors as Targets for Novel Analgesics and Anti-inflammatory Drugs. The Receptors 2014, 26: 239-254. DOI: 10.1007/978-1-4939-1167-7_12.Peer-Reviewed Original ResearchPositive allosteric modulatorsNicotinic receptorsNovel analgesicsTherapeutic windowChronic inflammatory pain conditionsAllosteric modulatorsInflammatory pain conditionsRecent animal studiesNarrow therapeutic windowPeripheral nervous systemAnti-inflammatory drugsAnalgesic efficacyPain controlPain conditionsΑ7 agonistsImmune cellsSelective α4β2Animal modelsHuman studiesAnimal studiesNervous systemNicotinic agentsTherapeutic potentialAgonistsAnalgesics