Bromocriptine-CB-154-free-base-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEBromocriptineCat.No.:HY-12705CASNo.:25614-03-3Synonyms:CB-154freebase分?式:C??H??BrN?O?分?量:654.59作?靶點(diǎn):DopamineReceptor作?通路:GPCR/GProtein;NeuronalSignaling儲存?式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY?物活性Bromocriptine?種有效的多巴胺D2/D3受體激動劑，結(jié)合多巴胺D2受體，pKi為8.05±0.2。IC50&TargetpKi:8.05±0.2(dopamineD2receptor)[1]體外研究Bromocriptinestimulates[35S]-GTPγSbindingatD2dopaminereceptorexpressedinCHOcellswithpEC50of8.15±0.05[1].Bromocriptinealsoisastronginhibitorofbrainnitricoxidesynthase.TheergotalkaloidBromocriptine(BKT)isfoundtoactasastronginhibitorofpurifiedneuronalnitricoxidesynthase(NOS)(IC50=10±2μM)whereasitispoorlyactivetowardsinduciblemacrophageNOS(IC50>100μM)[2].BromocriptineisfoundtoinhibittheactivityofatleastonehumancytochromeP450enzyme.BromocriptineisapotentinhibitorofCYP3A4withacalculatedIC50valuefortheinteractionof1.69μM[3].體內(nèi)研究Bromocriptine(adopamineagonist)treatment(2mg/kg,i.p.)groupshowssignificantanti-immobilityactionascomparedtocontrol.WhenBromocriptineadministered30minafterthelastdoseof7daysMPEtreatmentandsubjectedtoFST,thisdopaminergicagonistproducessignificantanddosedependentpotentiationofanti-immobilityactionofMPE(200mg/kg,p.o.)ascomparedtoMPEtreatmentalone.Bromocriptine(adopamineagonist)treatment(2mg/kg,i.p.)groupshowsasignificantreductionofimmobilitytimeascomparedtocontrol.Bromocriptineadministrationafter7dayspretreatmentwithMPE(100and200mg/kg,p.o.)showssignificantanddosedependentpotentiationofanti-immobilityactionofMPEascomparedtoMPEtreatmentalone[4].IntraperitonealadministrationofBromocriptineinducesasignificant,dosedependent(0.1mgand1mg/Kg)decreaseinpainscoresinCCI-IoNgroupwhencomparedtoshamanditseffectlastedfor6h.Thehighestdoseinducesthehighestscoredecrease,(P[5].1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEPROTOCOLKinaseAssay[1]The[35S]-GTPγSbindingassayiscarriedout.Cellmembranes(25±75ug)areincubatedinBufferBcontaining0.1mMdithiothreitol(DTT)and1uMGDPanddrugsinavolumeof0.9mLfor30minat30°C.Thispreincubationensuresthattheagoniststestedareatequilibriumwhenthe[35S]-GTPγS(50±150pM,finalconcentration)isadded(in100uLofBufferB)toinitiatethereaction.Theassaymixtureisincubatedforafurther20minunlessotherwisestated.Theassaysareterminatedbyrapidfiltrationandboundradio-activitydeterminedasdescribedfortheradio-ligandbindingassaysabove.Thetotalbindingof[35S]-GTPγSislessthan20%ofthatadded[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice[4]Administration[4][5]Swissmice(20-25g)ofeithersex(total150)areused.Bromocriptinemesylateisusedasdopaminereceptor(D2)agonist.Haloperidolisdilutedindistilledwaterwhichisusedforavehicleofinjection.Bromocriptinemesylateisdissolvedinonedropofglacialaceticacidandmadeuptovolumeindistilledwater.Imipramineisdissolvedin0.9%normalsaline.Haloperidol(0.1mg/kg,i.p.)andBromocriptinemesylate(2mg/kg,i.p.)areadministeredfor7daysingroupsofmiceinForcedSwimmingTest(FST)andTailSuspensionTest(TST).Imipramine(10mg/kg,p.o.)asastandardisadministeredinpositivecontrolgroupsfor7days.Rats[5]AdultmaleSprague-Dawleyrats(N=112,275-325g)areused.Twoweeksafterthe6-OHDAinjection,theanimalsarebriefly(<3min)anesthetizedwith2%halothaneusingamaskandreceivedforintracisternaladministrationBromocriptine(7μg/kgdissolvedin5μLvehicle)orthevehiclealone(5μLof0.9%saline).Fori.p.injectionweusedBromocriptine(1mg/kg)andSKF81297(3mg/kgdissolvedin0.9%saline)concentrations.Followingarecoveryperiod(<2min),theratsareplacedintheobservationfieldfor40minperiod-testbyablind-experimenter.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?NatCommun.2020Feb18;11(1):941.?SciAdv.2021Nov26;7(48):eabj4624.?BrJPharmacol.2021Apr26.?JEthnopharmacol.2021Mar9;113994.?BMCEndocrDisord.2021Nov23;21(1):235.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].GardnerB,etal.AgonistactionatD2(long)dopaminereceptors:ligandbindingandfunctionalassays.BrJPharmacol.1998Jul;124(5):978-84.2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE[2].RenodonA,etal.Bromocriptineisastronginhibitorofbrainnitricoxidesynthase:possibleconsequencesfortheoriginofitstherapeuticeffects.FEBSLett.1997Apr7;406(1-2):33-6.[3].WynaldaMA,etal.AssessmentofpotentialinteractionsbetweendopaminereceptoragonistsandvarioushumancytochromeP450enzymesusingasimpleinvitroinhibitionscreen.DrugMetabDispos.1997Oct;25(10):1211-4.[4].RanaDG,etal.DopaminemediatedantidepressanteffectofMucunapruriensseedsinvariousexperimentalmodelsofdepression.Ayu.2014Jan;35(1):90-7.[5].DiebW,etal.Nigrostriataldopaminergicdepletionincr