乙酰胆碱受体杀虫剂药理学.ppt

1、1,第七章、作用于ACh受体的杀虫剂,2,1. nerve impulse arrives 2. voltage-gated Ca2+ channels open 3. Synaptic vesicles fuse with plasma membrane and dump contents 4. Signalling molecule causes response in postsynaptic membrane,Sequence of events,3,二、氯化烟酰、沙蚕毒素类杀虫剂,4,作用于乙酰胆碱受体的杀虫剂,5,作用于乙酰胆碱受体的杀虫剂,乙酰胆碱受体是一种神经递质介导的离子通道

2、受体，由5个同源亚基组成。乙酰胆碱受体包括肌肉型和神经型两种。肌肉型乙酰胆碱受体是肌肉神经传导中的重要媒介物质以及自身免疫疾病重症肌无力的主要免疫原,神经型乙酰胆碱受体的突变也可导致某些疾病的发生。,6,作用于乙酰胆碱受体的杀虫剂,尼古丁之所以会让人上瘾，是因为它模仿某种使人觉得愉快的化学物质乙酰胆碱，“劫持”了大脑中与乙酰胆碱结合的受体蛋白质。乙酰胆碱受体可以分为多个亚单位，科学家已经发现了12个这样的亚单位 。一个称为a4*的乙酰胆碱受体亚单位在尼古丁成瘾过程中起到关键作用。,7,Nicotine, in the form of tobacco extract, has been used

3、 as an insecticide since the mid-eighteenth century and still ranks as an excellent contact insecticide. Plant insecticide Botanical insecticide,1 Nicotine,8,Nicotine attacks acetylcholine receptors, which resemble cholinesterases. Nicotine selectively attacks the neuromuscular junction of mammals a

4、nd the synaptic ganglion of insects without severely attacking other known acetylcholine receptors.,1 Nicotine,9,Nicotine AChR (acetylcholine receptor) Sodium Channel Open Sodium Influx Nerve Impulse,1 Nicotine,10,The most conspicuous feature of nicotine poisoning in insects is its selective inhibit

5、ory actions on nerve ganglia and synapses. It appears that nicotine is very selective in choosing the binding sites in both insects and mammals.,1 Nicotine,11,Nicotine selectively attacks the neuromuscular junction of mammals and the synaptic ganglia of insects without severely attacking other known

6、 acetylcholine receptors or the acetylcholinesterase, which is known to be similar in protein structure to the acetylcholine receptors.,1 Nicotine,12,Nicotine can mimic the action of acetylcholine in vivo under the proper conditions. It is likely that the receptors susceptible to nicotine cannot dis

7、tinguish between acetylcholine and nicotine.,1 Nicotine,13,本剂为植物源杀虫剂，其有效杀虫成分为由烟草中提取的烟碱。纯品为无色油状液体，性质不稳定。易挥发，能溶于水和有机溶剂。遇光和空气易变成褐色，有奇臭味和强烈刺激性。对害虫有胃毒、触杀和熏蒸作用，还有杀卵作用。烟碱易挥发，故残效期较短，而它的盐类（如硫酸烟碱）则较稳定，残效期长。,1 Nicotine,14,2 Imidacloprid(吡虫啉),Chloronicotinyl insecticide(氯化烟酰类杀虫剂) Because of high mammalian toxic

8、ity and relatively low insecticidal activity nicotine itself has not been widely used as a pesticide since the 1940s.,15,2 Imidacloprid(吡虫啉),Beginning with nithiazine in 1979 some related synthetic substance reacting at the same receptor as nicotine were discovered. Imidacloprid was introduced in 19

9、92 as a new neonicotinoid insecticides.,16,2 Imidacloprid(吡虫啉),Imidacloprid has similarities to nicotine and a comparable mode of action. It is active against sucking insects because of the unique plant-systemic and translaminar properties.,17,2 Imidacloprid(吡虫啉),Mode of action It appears that imida

10、cloprid acts in a way that is comparable to the action of acetylcholine on specific nerve cell. The favorable selective toxicity of imidacloprid to insects versus mammals is attributed to differences in their binding affinity or potency in the nicotinic acetylcholine receptor.,18,2 Imidacloprid(吡虫啉)

11、,Mode of action It appears that this binding-site specificity for imidacloprid depends in large part on major structural differences in the neuronal nicotinic acetylcholine receptor binding sites of mammals and insects.,19,2 Imidacloprid(吡虫啉),Mode of action This selectivity of the chloronicotinyl co

12、mpounds for insects as opposed to mammals can be partly explained by differences in the ionization of the pyrolidine nitrogen. Imidacloprid is poorly ionized in the neutral media, in contrast to nicotine, and thus passes easily through insect lipophilic barriers.,20,吡虫啉特点：超高效、低毒、广谱，对各类蚜虫有特效。药后3天防效达9

13、8%。持效期长，可达30天以上。适用范围广，用药量低。杀虫机理独特，同时具备触杀、胃毒、内吸传导三种功能，使害虫中枢神经阻断麻痹后迅速死亡。无交叉抗性，对人畜安全，能有效保护天敌。,2 Imidacloprid(吡虫啉),21,Animal toxicity Imidacloprid exhibits moderately acute oral toxicity to mammals with LD50 values of approximately 450 and 150 mg/kg bw in rat and mice, respectively. Mutagenicity tests were negative.,2 Imidacloprid(吡虫啉),22,1934年日本人从沙蚕中分离出沙蚕毒素（Nereis toxin），1962年确定其化学结构：,3 沙蚕毒素类杀虫剂,23,特点 1、多数具内吸作