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 ResearchMeSH KeywordsAllosteric RegulationAnimalsDisease Models, AnimalHydrocarbons, BrominatedIndole AlkaloidsMaleMiceNeuralgiaNicotineNicotinic AgonistsReceptors, NicotinicConceptsPositive 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 propertiesPersistent 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 laevis
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 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