阿维菌素类药物的研究进展

,2000,31(6),5202529ActaVeterinariaetZootechnicaSinica,,(,100094):(Avermectins),Eprinomectin,,Milbemycins:;;;;;;;:S85918:A:036626964(2000)0620520210:1999203214:(1964),,,,,,40,5,40(Phenothiazine)70(Oxfendazole),,(600mg/kg5mg/kg)1976(Avermectins)AvermectinsStreptomycesavermitilis,8,mg/kgg/kg(AvermectinB1,AVMAbamectin)(Ivermectin,IVM22,23dihydroavermectinB1)(Doramectin25cyclo2hexylavermectinB1)[1]Eprinomectin[2]Avermectins,,,20[3]1Avermectins,Avermectins,:(C2C8),(C13)(C17C28)[3]1Aver2mectins8C5,C22C23C25,A,B;1,2a,b,BA,B1B2[4]ab,a,80%,b20%,AVMB1aB1b(B1a80%,B1b20%)Avermectins,,,,(0100601009mg/L)[5]Avermectins,,C13,,,891011[6],AvermectinsIVMDoramectinEprinomectin3IVMwilkinsonC22C23,22,23dihydroavermectinB1IVMAVM,AVM[4]Doramectin(Mutationalbiosynthesis)C25,25cyclo2hexylavermectinB1DoramectinIVM,,AUC[7]Eprinomectin4-NHCOCH3,EprinomectinB1aB1b(B1a90%,B1b10%),[8]IVM,IVM,,[3],,24H2B1aH2B1b,2OH2B1aH2B1bAlvinerie(1994),3O,,Eprinomectin[8],10%,Avermectins[9],,2%[10]Avermectins,Toutain(1988),18d5146%IVMBogan(1988)[1],IVM200g/kgb.w.,AUC(872ng.h/ml)AUC(811ng.h/ml)4%EprinomectinNHCOCH3,(,Eprinomectin/(M/P)0117,IVMM/P=0177),Eprinomectin[28]2Avermectins,,,350r=5A(015nm),/115310IVM874(r=016nm),/3155,,,,1256:225311Fig.1Structureofavermectins,,Avermectins,[3](Haemonchuscontorus),,Avermectins(Haematopinuseurysternus,Linognathusvituli)(Damaliniabovis)[12]Avermectins(=510-6M),Avermectins(Gammaaminobutyricacid,GABA)GABA,GABACl-,GABAAvermectins,,(210-12M),AvermectinsGABACl-,AvermectinsCl-,Cl-,Cl-,,,[3413]Avermectins,CampbellBenz(1984)[14]GABAShoop(1993)[15],Cl-,AvermectinsAvermectins,,GABA,,,Cl-,Avermectins[3]3256:3Avermectins,,Avermectins[3]Avermectins4,Avermectins,IVM(Sustained2releasebo2lus,SRB)(Pour2on)[3],Doramectin[1617],AVMEprinomectin[2],,5511Avermectins,Avermectins(D.viviparus)(50g/kgb.w.),[18]IVMDoramectin,[11819],,[11]AvermectinsIVM,,512AvermectinsIVMAVMIVMNematodirusbattus,,,(7d)[12]513AvermectinsIVMIVMTrichurissuis,IVMTrichurissuisIVM013mg/kgb.w.011mg/kgb.w.,7d[3],AVMAscarissuumSar2coptesscabiei,Trichurissuis514AvermectinsIVMIVMCyathostomes99%,(EL3)(LL3/L4)[2021]IVM(Dictyocaulusarnifieldi)[22]O.cervicalis[23],Gasterophilusspp9514%[24]42531515AvermectinsIVMToxocaracanis,Toxascarisleonina,Ancylostomacaninum,Ancylostomabrasiliensis,UncinariastenocephalaTichurisvulpis(Collie)IVM,,IVM[3]6,,,11Table1ReportsofresistancetoavermectinsinnematodesofsheepandgoatsNematodespeciesAnimalspeciesDrugCountryReferenceHaemonchuscontortusSheepIVMAustraliaLejambre(1993)SheepIVMBrazilEchevarria&Trindade(1989)SheepIVMVieiraetal.(1992)DoramectinSantosetal.(1995)IVMSouthAfricaCarmichaeletal.(1987)IVMVanWyk&Malan(1988)IVMVanWyketal.(1989)SheepIVMUSACraig&Miller(1990)Ostertagiaspp.SheepIVMAustraliaSwanetal.(1994)GoatsIVMNZWatson&Hosking(1990)IVMBadger&Mckenna(1990)IVMLeathwick(1995)GoatsIVMUKJacksonetal.(1992)Trichostrongylusspp.GoatsIVMNZMckennaetal.(1990)GoatsIVMPomroyetal.(1992)3Mckellar&Benchaoui,1996.,C.elegans,IVM[3]7,AvermectinsGABA,GABAGABA,,(AvermectinsGABA5256:510-6M),,,,,,,,(LD50),IVM,25mg/kg,50mg/kg,Beagle80mg/kg,collie0101215mg/kgMurrayGreyAVM,(No2effectlevels,NOEL),014mg/kg/d015mg/kg/d112mg/kg/d,(),IVM,,2,,AmesDNA,IVMAVM,[25]8AvermectinsMilbemycinsMilbemycinsStreptomycescyaneogriseusStreptomyceshygroscopicus,MilbemycinsAvermectins,,80Sakamoto(1984)Tagawa(1985)MilbemycinDDirofilariaimmitis,Moxidectin(MXD)Milbemycinoxime[34]AvermectinsMilbemycins,MilbemycinsAvermectinsC13MXDNe2madectin,C23=N-COCH3MilbemycinOxime,80%A3(C25)20%A4(C25),C5=NOHMilbemycins,,,MXDC29/30C14(Hydroxymethyl),OMXD,(3%)[26],MXD,[27]MXDIVM,IVM(2)Alvinerie(1997)[28],(012mg/kgb.w.)MXD,,,IVM;MXDAUC(AUC2373136ng.h/ml,AUC2695192ng.h/ml),IVM(IVMAUCAUC)MXDIVMPerez(1997)[29]MXD(014mg/kgb.w.)IVM(012mg/kgb.w.),,MXDAUC(3631662531ng.d/ml)IVM(AUC=13217ng.d/ml),,MXD(MXDIVMMRT18142417d)2Ivermectin3Moxidectin33Table2Totaltissueresiduelevelsanddepletionhalf-livesofunchangeddrugincattletreatedwithIVM(013mg/kg,S.C.)ormoxidectin(012mg/kg,S.C.)DrugT1/2(d)LiverFat7,1428(p.p.b)LiverMuscleFat714287142871428IVM417413782551123202708329MXD9101210121015102097731211048986362753IVM013mg/kgb.w.33MXD012mg/kgb.w.,,MXD[242730]Milbemycinoxime,,015mg/kgb.w.milbemycinoximeA.cainum,collie,C5=NOH,,[4]AvermectinsMilbemycins,,,Craig(1992)Pankavich(1992),MXDIVMHaemonchuscontortus(012mg/kgb.w.,9919%,100%)MXDIVM,Shoop(1993)[15]Conder(1993),IVMMXDShoop,,MXDIVMOstertagiacircumcinctaTrichostrongyluscolubriformis,95%,IVM0102201032mg/kgb.w.,MXD01004701014mg/kgb.w.,MXDIVM,,IVMO.circumcinctaT.colubriformis,MXD31(01148mg/kgb.w.)9(01127mg/kgb.w.)95%,,IVMMXD,MXD(012mg/kgb.w.),IVM95%,,MXDIVMConder(1993),MXD0100125mg/jird,IVMH.contortus4712%,,MXD98%,,MXDIVM,Leathwick(1995)NemadectinIVM,,AvermectinsMilbemycins,7256:,,,IVM,MXD,,,:[1]GoudieAC,EvansNA,GrationKAF,etal.Doramectin-apotentnovelendectocid[J].VeterinaryPara2sitology,1993,49,515.[2]ShoopWL,etal.Eprinomectin:anovelavermectinforuseasatopicalendectocideforcattle[J],InternationalJournalParasitology,1996,26(11):12371242.[3]MckellarQA,BenchaouiHA.Avermectinsandmilbermycin