新煙(yan)堿類農藥是繼有機磷類、氨基甲酸酯(zhi)類、擬除蟲(chong)菊酯(zhi)類殺蟲(chong)劑(ji)(ji)(ji)之后(hou)的(de)第四代殺蟲(chong)劑(ji)(ji)(ji)，隨(sui)著高毒(du)農藥在全球市場的(de)退(tui)出，新煙(yan)堿類殺蟲(chong)劑(ji)(ji)(ji)逐(zhu)漸成為防治刺吸(xi)式口器害蟲(chong)、小型鱗翅目和鞘翅目害蟲(chong)最(zui)有效的(de)一類殺蟲(chong)劑(ji)(ji)(ji)。

據相關文(wen)獻報道(dao)，部分(fen)新煙(yan)堿類(lei)(lei)(lei)農藥(yao)對(dui)蜜(mi)蜂(feng)的(de)急性(xing)毒性(xing)為(wei)高毒或劇毒，會導(dao)致蜜(mi)蜂(feng)種群(qun)減(jian)少(shao)，存(cun)活與繁殖(zhi)能(neng)力降(jiang)低；甚至有(you)報道(dao)稱，新煙(yan)堿類(lei)(lei)(lei)農藥(yao)對(dui)土壤(rang)生態系(xi)統代表生物蚯蚓高毒。因此2020年來不斷有(you)國(guo)家組織傳來取消新煙(yan)堿類(lei)(lei)(lei)產(chan)品(pin)登記或禁使用(yong)新煙(yan)堿類(lei)(lei)(lei)產(chan)品(pin)的(de)禁令。另外，新煙(yan)堿類(lei)(lei)(lei)農藥(yao)的(de)抗性(xing)問題也是阻止(zhi)其(qi)進一(yi)步發展的(de)絆(ban)腳(jiao)石，但作(zuo)為(wei)當(dang)今全球最大的(de)一(yi)類(lei)(lei)(lei)植物源殺蟲劑，其(qi)優秀的(de)防治效果，在短時間內還無法找到替代的(de)產(chan)品(pin)。

1、發展歷史

自從1978年soloway等報道了(le)(le)具有殺蟲(chong)活(huo)性的硝基亞甲基雜環化合物(wu)以來，通過對該類化合物(wu)官(guan)能團的變換，20世(shi)紀(ji)80年代中(zhong)期德國拜耳公司(si)成功開(kai)發(fa)出(chu)第一個煙堿類農(nong)(nong)藥(yao)——吡(bi)蟲(chong)啉(lin)，其(qi)新穎的作用方式、選(xuan)擇(ze)毒性強、高效、廣譜和(he)對環境相(xiang)容(rong)性好(hao)等特點，立即引起(qi)了(le)(le)人(ren)們的注意，國外一些大的農(nong)(nong)藥(yao)公司(si)相(xiang)繼進入(ru)了(le)(le)煙堿類似(si)物(wu)研(yan)究領域，參與(yu)了(le)(le)此類化合物(wu)的合成研(yan)究，從而使其(qi)成為殺蟲(chong)劑研(yan)究開(kai)發(fa)的一大熱點。

煙(yan)(yan)(yan)(yan)堿(jian)作為(wei)殺(sha)(sha)蟲(chong)(chong)(chong)(chong)(chong)(chong)劑(ji)使用的(de)(de)(de)歷史可以追溯到(dao)17世紀，最初人(ren)類用煙(yan)(yan)(yan)(yan)草浸取液作為(wei)殺(sha)(sha)蟲(chong)(chong)(chong)(chong)(chong)(chong)劑(ji)。1828年(nian)(nian)確定該浸取液有(you)(you)效(xiao)成分(fen)為(wei)煙(yan)(yan)(yan)(yan)堿(jian)（S-nicotine），1904年(nian)(nian)成功合(he)成出煙(yan)(yan)(yan)(yan)堿(jian)。煙(yan)(yan)(yan)(yan)堿(jian)作為(wei)殺(sha)(sha)蟲(chong)(chong)(chong)(chong)(chong)(chong)劑(ji)主要用于防治(zhi)果(guo)樹、蔬菜(cai)和(he)(he)水(shui)稻等的(de)(de)(de)害(hai)蟲(chong)(chong)(chong)(chong)(chong)(chong)，去甲煙(yan)(yan)(yan)(yan)堿(jian)（nornicotine）和(he)(he)毒(du)(du)藜堿(jian)（anabasine）也曾有(you)(you)一定范(fan)圍(wei)的(de)(de)(de)使用。1970年(nian)(nian)殼牌發(fa)(fa)展(zhan)公司先后發(fa)(fa)現(xian)化(hua)合(he)物(wu)(wu)(wu)SD-031588[2-(二溴硝(xiao)甲基(ji)(ji))-3-甲基(ji)(ji)吡(bi)(bi)啶]、SD-033420、SD-035347、SD-035651（即nithiazine，SKI-71）和(he)(he)噻(sai)蟲(chong)(chong)(chong)(chong)(chong)(chong)醛（WL-108477）等。這些(xie)化(hua)合(he)物(wu)(wu)(wu)雖然(ran)均存在(zai)(zai)(zai)較易(yi)水(shui)解、較差的(de)(de)(de)光穩定性(xing)(xing)、對(dui)哺(bu)乳(ru)動(dong)(dong)物(wu)(wu)(wu)毒(du)(du)性(xing)(xing)高等問題(ti)，但其較好的(de)(de)(de)生(sheng)物(wu)(wu)(wu)活性(xing)(xing)引起(qi)(qi)研究人(ren)員的(de)(de)(de)重視，拜耳公司于1984年(nian)(nian)將硝(xiao)蟲(chong)(chong)(chong)(chong)(chong)(chong)噻(sai)嗪結構衍生(sheng)出化(hua)合(he)物(wu)(wu)(wu)NTN32692，在(zai)(zai)(zai)此基(ji)(ji)礎上(shang)，吡(bi)(bi)蟲(chong)(chong)(chong)(chong)(chong)(chong)啉（imidacloprid）在(zai)(zai)(zai)1991年(nian)(nian)被成功開發(fa)(fa)上(shang)市(shi)。1993年(nian)(nian)，為(wei)將吡(bi)(bi)蟲(chong)(chong)(chong)(chong)(chong)(chong)啉等通過天然(ran)生(sheng)物(wu)(wu)(wu)堿(jian)結構優化(hua)得到(dao)的(de)(de)(de)殺(sha)(sha)蟲(chong)(chong)(chong)(chong)(chong)(chong)劑(ji)區別以前的(de)(de)(de)煙(yan)(yan)(yan)(yan)堿(jian)類殺(sha)(sha)蟲(chong)(chong)(chong)(chong)(chong)(chong)劑(ji)，提出了“新煙(yan)(yan)(yan)(yan)堿(jian)類”概念。吡(bi)(bi)蟲(chong)(chong)(chong)(chong)(chong)(chong)啉超高的(de)(de)(de)殺(sha)(sha)蟲(chong)(chong)(chong)(chong)(chong)(chong)活性(xing)(xing)，立即引起(qi)(qi)全球(qiu)范(fan)圍(wei)內類似(si)結構化(hua)合(he)物(wu)(wu)(wu)的(de)(de)(de)研發(fa)(fa)熱潮，開發(fa)(fa)出多個高效(xiao)殺(sha)(sha)蟲(chong)(chong)(chong)(chong)(chong)(chong)劑(ji)，目前在(zai)(zai)(zai)全球(qiu)范(fan)圍(wei)內開發(fa)(fa)和(he)(he)使用的(de)(de)(de)新煙(yan)(yan)(yan)(yan)堿(jian)類農(nong)藥主要有(you)(you)12種。新煙(yan)(yan)(yan)(yan)堿(jian)類和(he)(he)煙(yan)(yan)(yan)(yan)堿(jian)類殺(sha)(sha)蟲(chong)(chong)(chong)(chong)(chong)(chong)劑(ji)作用機理相同，區別在(zai)(zai)(zai)于兩者(zhe)(zhe)的(de)(de)(de)選(xuan)擇性(xing)(xing)差異大(da)，前者(zhe)(zhe)殺(sha)(sha)蟲(chong)(chong)(chong)(chong)(chong)(chong)活性(xing)(xing)高、對(dui)哺(bu)乳(ru)動(dong)(dong)物(wu)(wu)(wu)低(di)毒(du)(du)，后者(zhe)(zhe)殺(sha)(sha)蟲(chong)(chong)(chong)(chong)(chong)(chong)活有(you)(you)限(xian)、對(dui)哺(bu)乳(ru)動(dong)(dong)物(wu)(wu)(wu)毒(du)(du)性(xing)(xing)高。

2、作用機理

新(xin)煙堿(jian)(jian)類殺(sha)(sha)蟲(chong)(chong)劑(ji)(ji)的(de)(de)作(zuo)用(yong)機(ji)理(li)是(shi)其(qi)作(zuo)為煙堿(jian)(jian)乙(yi)酰膽(dan)(dan)堿(jian)(jian)受體（nAChRs）激動(dong)劑(ji)(ji)與(yu)乙(yi)酰膽(dan)(dan)堿(jian)(jian)受體選擇(ze)性(xing)結(jie)合，與(yu)昆蟲(chong)(chong)乙(yi)酰膽(dan)(dan)堿(jian)(jian)（ACh）產生競爭，阻斷(duan)中樞神(shen)經正常(chang)傳(chuan)導(dao)，進而導(dao)致昆蟲(chong)(chong)麻痹、死亡(wang)。由于該類殺(sha)(sha)蟲(chong)(chong)劑(ji)(ji)具有獨特的(de)(de)作(zuo)用(yong)機(ji)制，與(yu)常(chang)規殺(sha)(sha)蟲(chong)(chong)劑(ji)(ji)沒有交互抗性(xing)，其(qi)不僅具有高效、廣譜及良(liang)好(hao)的(de)(de)根部內吸性(xing)、觸殺(sha)(sha)和胃毒作(zuo)用(yong)，而且對(dui)哺乳動(dong)物(wu)毒性(xing)低，可有效防(fang)治同翅(chi)(chi)目(mu)(mu)、鞘(qiao)翅(chi)(chi)目(mu)(mu)、雙翅(chi)(chi)目(mu)(mu)和鱗翅(chi)(chi)目(mu)(mu)等害蟲(chong)(chong)，對(dui)用(yong)傳(chuan)統殺(sha)(sha)蟲(chong)(chong)劑(ji)(ji)防(fang)治產生抗藥性(xing)的(de)(de)害蟲(chong)(chong)也有良(liang)好(hao)的(de)(de)活(huo)性(xing)。新(xin)煙堿(jian)(jian)類殺(sha)(sha)蟲(chong)(chong)劑(ji)(ji)既可用(yong)于莖葉處理(li)，也可用(yong)于土壤、種子處理(li)。相對(dui)而言，新(xin)煙堿(jian)(jian)類殺(sha)(sha)蟲(chong)(chong)劑(ji)(ji)是(shi)一類高效、安全、高選擇(ze)性(xing)的(de)(de)新(xin)型殺(sha)(sha)蟲(chong)(chong)劑(ji)(ji)。

3、結構

從新(xin)煙堿(jian)類農(nong)(nong)藥(yao)的結(jie)構來看(kan)，目前有(you)2種(zhong)分類的方法：①根據環狀(zhuang)結(jie)構將現有(you)的新(xin)煙堿(jian)類農(nong)(nong)藥(yao)分為(wei)(wei)兩種(zhong)系統(tong)(tong)，即五(wu)(wu)元(yuan)環和(he)六元(yuan)環系統(tong)(tong)，五(wu)(wu)元(yuan)環和(he)非環狀(zhuang)系統(tong)(tong)；②根據取代(dai)(dai)(dai)基的不同將新(xin)煙堿(jian)類農(nong)(nong)藥(yao)分為(wei)(wei)三代(dai)(dai)(dai)，第(di)(di)一(yi)代(dai)(dai)(dai)為(wei)(wei)氯代(dai)(dai)(dai)煙堿(jian)型(xing)，第(di)(di)二代(dai)(dai)(dai)為(wei)(wei)硫(liu)代(dai)(dai)(dai)煙堿(jian)型(xing)，第(di)(di)三代(dai)(dai)(dai)為(wei)(wei)呋喃型(xing)，這也是新(xin)煙堿(jian)類農(nong)(nong)藥(yao)的發展過程。

4、主要產品開發情況

目(mu)前，在全球范圍內(nei)開發(fa)或已(yi)使用的新煙堿(jian)類農藥(yao)主要有13種，詳(xiang)細信息(xi)見表1。

表1新煙堿類農藥品種(zhong)信息

5、新煙堿農藥在我國登記劑型分析

農藥的(de)(de)原藥一般(ban)不能直接在生產上使(shi)用，通常需經過(guo)加工配制(zhi)成各種類型的(de)(de)制(zhi)劑(ji)。新頒(ban)布(bu)的(de)(de)GB/T 19387—2017《農藥劑(ji)型名稱及代(dai)碼》對農藥劑(ji)型重新進行了科學分類，目前我國的(de)(de)農藥劑(ji)型共有61種。

5.1、登記劑型品種繁多

新煙(yan)堿類農(nong)藥(yao)目前(qian)在我國登記的(de)劑(ji)(ji)(ji)型有38種，共登記3 209個產品(pin)。占到我國農(nong)藥(yao)劑(ji)(ji)(ji)型的(de)62.3%。其中可濕性粉劑(ji)(ji)(ji)694個，乳油463個，水(shui)分散粒劑(ji)(ji)(ji)449個，懸浮劑(ji)(ji)(ji)295個等（表(biao)2）。

表(biao)2新煙堿類農藥目(mu)前(qian)在我國登記的劑型及數(shu)目(mu)匯總

5.2、環(huan)境友(you)好型劑型品種(zhong)較多

隨著科(ke)技的進步和國家農(nong)藥管理的深入，農(nong)藥劑型的研發以高效、安全、環(huan)(huan)保、方便為(wei)主要目標(biao)，向(xiang)水基化(hua)、顆粒(li)化(hua)、低毒化(hua)、多(duo)功(gong)能化(hua)方向(xiang)發展，新煙堿類農(nong)藥環(huan)(huan)境(jing)友好農(nong)藥占到已登記農(nong)藥品種(zhong)的59%以上，以懸(xuan)浮劑、水分散(san)粒(li)劑、懸(xuan)浮種(zhong)衣劑等環(huan)(huan)保劑型作為(wei)農(nong)藥制劑主體。

6、新煙堿類農藥發展存在的問題

新煙堿類農藥的(de)發展近幾年遇到了嚴(yan)重(zhong)的(de)瓶頸，尤其是在毒性(xing)和(he)抗性(xing)方面。據(ju)相(xiang)關報道新貴氟吡呋喃(nan)酮在我國褐飛虱田間種群(qun)已產生中等水(shui)平抗性(xing)。

6.1、毒性

隨著高毒農藥(yao)(yao)在全球市場的(de)退出，新(xin)煙(yan)(yan)堿類(lei)殺(sha)蟲(chong)(chong)(chong)(chong)劑逐漸成(cheng)為(wei)防治刺吸(xi)式口器害(hai)蟲(chong)(chong)(chong)(chong)、小型鱗翅(chi)目(mu)和鞘(qiao)翅(chi)目(mu)害(hai)蟲(chong)(chong)(chong)(chong)最有(you)(you)效(xiao)的(de)一類(lei)殺(sha)蟲(chong)(chong)(chong)(chong)劑。但近年(nian)來，研究者(zhe)們發現，部分(fen)新(xin)煙(yan)(yan)堿類(lei)殺(sha)蟲(chong)(chong)(chong)(chong)劑（如(ru)吡(bi)(bi)蟲(chong)(chong)(chong)(chong)啉(lin)、噻(sai)蟲(chong)(chong)(chong)(chong)嗪、噻(sai)蟲(chong)(chong)(chong)(chong)胺(an)(an)、呋蟲(chong)(chong)(chong)(chong)胺(an)(an)等(deng)）對(dui)蜜(mi)(mi)蜂的(de)急(ji)性毒性為(wei)高毒或劇毒，且具有(you)(you)亞(ya)致死效(xiao)應；有(you)(you)效(xiao)成(cheng)分(fen)及代謝物在花粉和花蜜(mi)(mi)中殘留(liu)，導致蜜(mi)(mi)蜂種(zhong)(zhong)群減少，存活與繁殖(zhi)能力降低(di)；此(ci)外(wai)(wai)，吡(bi)(bi)蟲(chong)(chong)(chong)(chong)啉(lin)、啶蟲(chong)(chong)(chong)(chong)脒、烯啶蟲(chong)(chong)(chong)(chong)胺(an)(an)、噻(sai)蟲(chong)(chong)(chong)(chong)胺(an)(an)、噻(sai)蟲(chong)(chong)(chong)(chong)啉(lin)等(deng)還對(dui)土壤生(sheng)態系統代表生(sheng)物蚯蚓高毒。鑒于此(ci)，多個國家和組織對(dui)部分(fen)新(xin)煙(yan)(yan)堿類(lei)殺(sha)蟲(chong)(chong)(chong)(chong)劑的(de)環(huan)境(jing)風險進行再(zai)評價或限制使用，甚至(zhi)禁(jin)用。例如(ru)：歐盟成(cheng)員國于2018年(nian)5月通過投票(piao)，確定(ding)將于2018年(nian)年(nian)底(di)前禁(jin)止戶外(wai)(wai)施用對(dui)蜜(mi)(mi)蜂有(you)(you)害(hai)的(de)3種(zhong)(zhong)新(xin)煙(yan)(yan)堿類(lei)殺(sha)蟲(chong)(chong)(chong)(chong)劑（吡(bi)(bi)蟲(chong)(chong)(chong)(chong)啉(lin)、噻(sai)蟲(chong)(chong)(chong)(chong)胺(an)(an)和噻(sai)蟲(chong)(chong)(chong)(chong)嗪）；美國環(huan)境(jing)保護署(shu)取消了12種(zhong)(zhong)會傷害(hai)蜜(mi)(mi)蜂的(de)新(xin)煙(yan)(yan)堿類(lei)農藥(yao)(yao)產品(pin)(pin)登(deng)記，2019年(nian)5月20日起(qi)生(sheng)效(xiao)，包含先正達、拜耳(er)旗下產品(pin)(pin)。取消的(de)12項(xiang)產品(pin)(pin)登(deng)記中包含7項(xiang)種(zhong)(zhong)衣劑，含噻(sai)蟲(chong)(chong)(chong)(chong)胺(an)(an)、噻(sai)蟲(chong)(chong)(chong)(chong)嗪的(de)產品(pin)(pin)登(deng)記。

6.2、抗性

根(gen)據相關研(yan)究報(bao)道，新煙堿類農藥在(zai)防治(zhi)某(mou)些害蟲(chong)時不同程度(du)出(chu)現(xian)了抗(kang)(kang)(kang)藥性(xing)，對(dui)第(di)(di)1代新煙堿類藥劑(ji)吡蟲(chong)啉表(biao)現(xian)高水(shui)平(ping)(ping)抗(kang)(kang)(kang)性(xing)（抗(kang)(kang)(kang)性(xing)倍(bei)數(shu)＞1 000），對(dui)烯啶蟲(chong)胺(an)(an)表(biao)現(xian)低至(zhi)中等(deng)水(shui)平(ping)(ping)抗(kang)(kang)(kang)性(xing)（抗(kang)(kang)(kang)性(xing)倍(bei)數(shu)5.1～12）；對(dui)第(di)(di)2代新煙堿類藥劑(ji)噻蟲(chong)嗪表(biao)現(xian)高水(shui)平(ping)(ping)抗(kang)(kang)(kang)性(xing)（抗(kang)(kang)(kang)性(xing)倍(bei)數(shu)＞200）；對(dui)第(di)(di)3代新煙堿類藥劑(ji)呋蟲(chong)胺(an)(an)表(biao)現(xian)中等(deng)至(zhi)高水(shui)平(ping)(ping)抗(kang)(kang)(kang)性(xing)（抗(kang)(kang)(kang)性(xing)倍(bei)數(shu)24～201）。

7、結語

新(xin)煙堿類(lei)殺(sha)(sha)(sha)蟲(chong)劑(ji)由于其廣譜、高效、內吸好(hao)、且與常規(gui)農(nong)藥無交互抗性等(deng)特點，深受用(yong)戶喜愛，在殺(sha)(sha)(sha)蟲(chong)劑(ji)市場占(zhan)據了主(zhu)要地位(wei)。但是其暴(bao)露出(chu)來的(de)風險也應引起(qi)足夠重視，下(xia)一步開發(fa)農(nong)藥新(xin)產(chan)(chan)品(pin)時，需要解決(jue)相應問題(ti)，盡量(liang)開發(fa)出(chu)一些可替代(dai)產(chan)(chan)品(pin)或交替使用(yong)的(de)產(chan)(chan)品(pin)，近(jin)年來復配產(chan)(chan)品(pin)的(de)陸續上市或許會給新(xin)煙堿類(lei)殺(sha)(sha)(sha)蟲(chong)劑(ji)帶來新(xin)的(de)機會和活力。總之，新(xin)煙堿類(lei)殺(sha)(sha)(sha)蟲(chong)劑(ji)的(de)未(wei)來何(he)去(qu)何(he)從，只能且行且看。