作用于GABA受体杀虫剂药理学ppt课件

1 第六章作用于GABA受体杀虫剂 1 GABA receptorGABA aminobutyricacid isatrueneurotransmitter GABA sroleisthatoftheprimaryinhibitoryneurotransmitter GABAachievesthisbyeffectingtheactionsoftheGABAreceptor a5subunitiontransporter 2 1 GABA receptor 3 1 GABA receptor 4 1 GABA receptor 5 1 GABA receptor 6 1 GABA receptor WhenGABAbindstotheGABAreceptor thesubunitsofthereceptor open andthereisaninfluxofchlorideions Thisinfluxrestorestheelectricalpotentialoftheneuronandtherebydecreasesthelikelihoodthattheneuronwilldepolarizeandrelaytheincomingsignal Essentially weakorirrelevantsignalsaremorelikelytobeterminatedor ignored 7 2 fipronil 2 锐劲特 regent 氟虫腈fipronil 法国罗纳普朗克公司开发的苯并吡唑类杀虫剂 中等毒性 以触杀 胃毒为主 在水稻上内吸作用强 主要防水稻螟虫 飞虱 蓟马 蚜虫 小菜蛾等 对有机磷和菊酯类杀虫剂抗性害虫的防治效果较好 8 2 fipronil Fipronilisahighlyactive broad spectruminsecticidefromthephenylpyrazole 吡唑 family Itcanbeusedagainstmajorlepidopterousandorthopterouspestsonawiderangeoffieldandhorticulturalcropsandagainstcoleopterouslarvaeinsoil Itisalsoemployedforcockroachandantcontrol 9 2 fipronil Fipronilwasdiscoveredin1987andfirstauthorizedforagriculturalandno agriculturalusein1993 Themajoradvantagesincludeabroadspectrumofactivity lackofcross resistancewithexistingcommercialproducts andselectivityagainstpestspecies 10 2 fipronil ThemechanismofactionforthisinsecticideappearstobetheblockageoftheGABA regulatedchloridechannel Fipronilactsasaninsect specificantagonistalteringchlorideionflux resultingindisruptionofCNSactivityanddeathoftargetinsect 11 2 fipronil Insectspecificityrelativetomammalsistheresultofdifferencesinthebindingaffinityoffiproniltochloridechannelmembranes 12 2 fipronil AnimaltoxicityThegenotoxicitystudiesshowednomutagenicpotential Nocasesofadversehealtheffectsinhumanshavebeenreportedforfipronil 13 3 Avermectin Avermectinsareanewfamilyofinsecticidal acaricidal andantihelminthic 驱肠虫的 agentsthathavebeenisolatedfromfermentationproductsofStreptomycesavermitilis 14 3 Avermectin Thesecomplexmacrocyclicdisaccharideshaveshownbiologicalactivityagainstinsects nematodes andarthropods 15 3 Avermectin Abamectinwasdevelopedforagriculturaluse Itiscomposedof80percentavermectinB1aand20percentavermectinB1b 16 3 Avermectin Therelatedsubstance ivermectin wasintroducedintohumanmedicinemainlyforuseagainstOnchocercavolvulus 盘尾丝虫 andalsointoveterinarymedicineagainstanimalparasites 17 3 Avermectin 阿维菌素 英文名称为Avermectin 是一种新型农畜两用抗生素 属大环内酯抗生素类杀虫杀螨剂 是土壤微生物灰色链霉素 Strentomycesavermitilis 的发酵代谢产物 18 3 Avermectin 作用机理 Avermectins作用于昆虫神经元突触或神经肌肉突触的GABA A受体 激发神经未梢放出神经传递抑制剂 氨基丁酸 GABA 促使GABA门控的氯离子通道延长开放 对氯离子通道具有激活作用 大量氯离子涌入造成神经膜电位超级化 致使神经膜处于抑制状态 从而阻断神经未梢与肌肉的联系 使昆虫麻痹 拒食 死亡 19 3 Avermectin AnimaltoxicityAbamectincanbeconsideredtobeaspecificallyneurotoxicsubstanceviaopeningofGABA controlledchloridechannels 20 3 Avermectin AnimaltoxicityTheacuteoraltoxicityishighwithLD50valuesfrom1 5mg Kgbwinratsto85mg Kgbwinduckwithmainlyneurotoxicsymptoms Noevidenceofoncogenicpotentialhasbeenfoundinratsandmice Avermectinsexhibitnogenotoxicormutagenicpotential 21 3 Avermectin Sincecommerciallyavailableabamectinformulationsofpesticidescontainonlyalowamountoftheactiveingredient severeintoxicationsareonlypossibleifrelativelylargequantitiesoftheformulationareingested 22 4Spinosad 多杀菌素 Spinosadisanaturalfermentationproductproducedbytheactinomycetebacterium Saccharopolysporaspinosa Ithasinsecticidalactivityandhasastructureconsistingofalargecomplexhydrophobicring abasicaminegroup andtwosugarmoieties 23 4Spinosad 多杀菌素 Spinosadiscomposedofnumerousspinosyns butnearlyalloftheinsecticidalactivityofspinosadisproducedbythetwocloselyrelatedcompoundsspinosynsAandD inaratioofapproximately7 1 24 4Spinosad 多杀菌素 Spinosadhasproveneffectiveincontrollingmanychewinginsectpestswithsuchhighselectivitythatmorethan70percentofbeneficialinsectsandpredatorywaspsareleftunharmed 25 4Spinosad 多杀菌素 Insectsexposedtospinosadexhibitclassicalsymptomsofneurotoxicity includinglackofcoordination prostration tremors andotherinvoluntarymusclecontractionsleadingtoparalysisanddeath 26 4Spinosad 多杀菌素 Bio insecticidespinosadisanovelinsecticidewhichshowsthespecialneurotoxicpoisoningsymptomwithanelevationofthebody involuntarymusclecontractionsandtremors eventuallyprostrateandparalyzed 27 4Spinosad 多杀菌素 Althoughthemodeofactionofspiosadisnotfullyunderstood itappearstoaffectnicotinicandGABA receptorfunction 28 4Spinosad 多杀菌素 Spinosaddepolarizesinsectneuronsbyactivatingnicotinicreceptors causingwidespreadhyperactivityinthenervoussystem Spinosadalsoactat aminobutyricacidreceporsbyinhibiting aminobutyricacidreceporstoleadneuronshyperactive 29 4Spinosad 多杀菌素 AnimaltoxicitySpinosadisoflowacutetoxicityafteroralordermaladministrationandbyinhalation TheoralLD50is 2000mg Kgbwforratsandmice ThedermalLD50is 5000mg Kgbwforrabbits 30 4Spinosad 多杀菌素 AnimaltoxicityThemainhistopathologicaleffectsassociatedwithrepeatedexposuretospinosadinalltestspecieswerecellularvacuolation inflammatorychangesincludingnecrosis histiocytosis 组织细胞增多病 andregenerativeanddegenerativechangesinawiderangeoftissue 31 4Spinosad 多杀菌素 AnimaltoxicityIndevelopmentalstudies spinosadcauseddecreasedbodyweightsinmaternalratsandrabbits butthiswasnotaccompaniedbyembryo toxicity fetaltoxicity orteratogenicity 32 4Spinosad 多杀菌素 AnimaltoxicitySpinosaddidnotcasespecif