293 INDEX

A aconitine, 42,50 AAP (see acetamiprid) ActaraTM, 182 ABT-418, 241 acyclic cyanoamidine, 181 AC-303,630, 52 acyclic nitroamidine, 181 acephate, 158,159,160,161,163,167 acyclic nitroenamine, 181 acetamiprid, 9, 16, 18,19,22, 103,110,120,121, acyclic nitroethenes, 129 149,152,177,180,188,254,258 structure-activity relationship. 129 administration, 162 synthesis, 129 beneficials, effect on, 151 adaline,49 binding, 17, 164 Admire™, 115 (see imidacloprid) cross-resistance, 158 affinin, 34 ecotoxicity, 150 affinity chromatography, 279 electrophysiology, 164 AKD-1022, 179,180,181 field efficacy, 166-174, alkaloids, 29 insecticidal activity, 157,162,185 Aconitum, 42 lead generation, 152 amphibian, 50 mode of action, 164 arthropoda!, 48 persistency, 162 azocinoindole, 54 physical properties, 150 benzophenanthridine, 44 speed of action, 162 definition, 29 structure-activity relationship, 153-155 Delphinium, 42 synthesis, 156 dioxepineindole, 52 systemic action, 160,186 Erythrina, 45 toxicity to mammals, 150 haplophyton, 47 trans1aminar action, 160 isoquinoline-type, 44 acetogenins, 44 lupine, 33 (ACh), 6,223,276 marine, aquatic, 51 acetylcholine receptor(AChR), 3,24,122,123,237 microorganisms, 51 antagonists, 122 Nicotiana, 30,31 muscarinic (mAChR), 6,24,237,275 po1yhydroxy, 47 nicotinic (nAChR, see nicotinic quinolizidine, 33 acetylcholine receptor) Solanum, 38,39 acetylcholinesterase (AChE), Stenuma,46 inhibition, 6,39,40,47 steroid, 29 model for nAChR, 6 , 30 3-0-acety1zygadenine, 39 Trypterygium, 46 unsaturated amide, 34 294

Veratrum, 37 cartap. 51,127,159,254,255, 3-aminomethyl-6-chloropyridine. 156 castanosperrnine, 48 2-amino-5-methylpyridine, 112 cell, cell line, anabasamine, 32 BC3H I muscle cell, 278 , 4,5,32,48 Drosophila (S2). 286 , 4,5, 16,17,32,45 human embryonic kidney (HEK-293), anacyclin, 34 285,286 anatabine, 32 NIE-115 neuroblastoma. 278 anatoxin A, 120,121 cevacine, 38 3-0-angeloylzygadenine. 39 cevadine, 37 anonaine, 44 cevine, 37 6-aryl-2,4-hexadienamides, 36 COA 293'343, 177,180,181,205 6-aryl-3,5-hexadienamides, 36 beneficial arthropods, effect on, 202 aspernomine, 52 biological activity, 184 atropine, 276 14C-, 199 averrnectin, 123 chemical properties, 183 azadirachtin, 43 consumer safety, 204 azamacrolides, 49 crop tolerance, 201 1-aza-3-thiacycloalkanes, 79 discovery, 181 azinphosmethyl, 251 ecotoxicity, 205 environmental fate, 205 B field performance, 188-198,20 I foliar use, !89 batrachotoxin, 50 insecticidal spectrum, 185,187 Bay T 9992, Ill lasting activity, 199 ~enfuracarb, !58, 160, metabolism, 203,204 bensultap, 254,255 physical properties, 183 berberine, 44 residues, 204 a-BOT-ASA (see azidosalicylate derivative seed treatment use, 196 of a-BOT) soil application use, 194 bioaccumulation. I 04 synthesis, 183 I, 1-bis(methylthio)-2-nitroethylene, 273 systemicity, 186,199 BT, 163,167 toxicology, 203 BT0-502, 37 use rate, 20 I a-bungarotoxin (a-BOT), 17, 42, 120, 121, a-chaconine, 39 123,164,165,271,276,282 charatoxin, 51 buprofezin, 138,191,192,194 CH-IMI (see 6-Cl-PMNI, nitromethylene analog of imidacloprid) c 2-chloro-5-chloromethyipyridine (CCMP), Ca2• channel, 41,44 111,112,113 Ca2•-dependent ATPase, 50 6-chloro-3-(methylamino)methylpyridine, 156 Ca2• release, 40 2-chloro-5-methylpyridine (CMP), II I, I I 2 caffeine. 44 6-chloronicotinic acid, 112,2 I 3 , 17,276,282 6-chloronicotinoyl chloride, 272 carbofuran, 118 chloronicotinyl insecticides (see also 295

nicotinoids, imidacloprid analogs), 2,6-dialkylpiperidines, 48 10,91,105, 109,111,180,254 2,5-dialkylpyrrolidines, 48 biological performance, 113 2,5-dialkylpyrrolines. 48 resistance, 253,265 3,5-dialkylpyrrolizidines, 48 water solubility, 103 I ,3-diazacycloalkanes, 77,79 6-chloronicotinyl-2- 2-(dibromonitromethyl)-3-methylpyridine, 71 nitromethyleneimidazoline, 95 9,21-didehydroryanodine, 40 1-[ (4-ch loropheny !)methyl)-2-(nitromethyl)• dihydro p -erythroidine, 120,121 pyridinium hydroxide, 77 dihydronicotyrine, 4,5,7,32 chloropyridine, II 0,112 4,5-dihydro-N-nitro-1 H-imidazol-2-amine, 273 1-[ N-( 6-chloro-3-pyridylmethyl )-N• I 0, 11-dihydropipercide, 36 ethyl]amino-1-methylamino-2- dimethylphenylpiperazinium (DMPP), 17 nitroethane, 132 1,2- or 2.2-dimethylpropylamides, 36 N-( 6-chloro-3-pyridylmethyl)-ethylenediamise,273 dioncophyllines, 44,45 chlorpromazine, 17 dioxapyrrolomycin, 52 chlorpyrifos, 177 dipotassium 2-nitroethylene-1, 1-dithiolate, 78 Cl-TMNI (see chlorothiazoy1 analog ofCH-IMI) 3,2'-dipyridyl or 2,3'-bipyridyl (isonicoteine),4,32 cocaine, 43 I ,3-dithiane, 51 coccinelline, 49 1,2-dithiolane, 51 cocculolidine, 45 DN-IMI (see [lH]-desnitroimidacloprid) concanavalin A, 286 ConfidorTM, 114 (see imidacloprid) E coniine, 17 echinacein, 34 , 4,5,32 , 120,121,243,245,249,250 crooksiine, 47 epilachnene, 49 cross-resistance, imidacloprid and, erysodine, 45 carbamates, 257 eserine (see physostigmine) chloronicotinyls, 258 ethofenprox, 138 endosulfan, 257 1-ethyl-3-[3(dimethylamino)propyl)- management, 253,261-266 carbodiimide, 274.287 nAChR insecticides, 255 organophosphorus insecticides, 257 other insecticides, 257 F pyrethroids, 257 fagaramide, 35 Cruiser®, 182 (see CGA 293'343) fenitrothion, 103,138,171 N-cyano-N-methylacetamidine, 273 fenobucarb, 138 cypermethrin, 103,116,159,163,170, , 17,33, 120,121,282 G GABAA receptor, 123 D GauchoTM, 115 (see imidacloprid) DDT, 37 glaudelsine, 42 dehydrothalebanin B, 37 glomerins, 49 deltamethrin, 37,192 glucosidase inhibition, 48 3,5-dialkylindolizidines, 48 glutamate receptor, 33,123 296

guineensine, 36 287,288 guinesine A,B, 33 azidosalicylate derivative of a-BGT (a-BGT-ASA), 281,285,287,288 a-BGT, 279,285,286,287 imidacloprid (IMI), 9,10.11,12,18,19,20,21, 22,31 ,77,80,98,99, 100,101,102,103, batrachotoxinin A 20a-benzoate, 37 104,110,111,113,114,120,121,152, a-bungarotoxin (a-BGT), 13, 16, 23, 177,180,188,213,253,256,271,276 1'20, 121.164,273,275,276,277,278 acute toxicity, 216 6-chloro-3-chloromethylpyridine, 273 antifeedant effect, 115 2-chloro-5-chloromethylthiazole, 273 beneficial arthropods, activity on, 117 cytisine, 121 binding, 213 desnitroimidacloprid (DN-IMI}, 272 insect nAChR,12,16.17,120,123,275.277 epibatidine, 286 mammalian nAChR, 16,277, LiAPH4, 273 Torpedo nAChR, 17 3 Li8 H4, 273 biological performance,ll3, 185, 186, 187 Na83H4, 273 chronic toxicity, 216 (PCP), 16,23 developmental toxicity, 218 radiosynthesis, 272,274 ecobiological profile, 117 PHJ-nicotinoids excretion, 213 acetamiprid (AAP), 272 foliar application, 114,190,191,192,193,194 chlorothiazoyl analog of CH-IMI (Cl hazard assessment, 217,219,220 TMNI), 272,275,276 market, 109,lll,ll9 desnitroimidacloprid (DN-IMI), 272 metabolism, 213,215 imidacloprid (IMI}, 121,271,272,274, N-methyl-, 13,19,20 275,276,277,288 mode of action, 21 ,22,213 (NIC), 16,238,277,278,279 mutagenicity, 218 nitromethylene analog of imidacloprid neurotoxicity, 220 (CH-IMI), 272,279 oncogenicity, 218 radiosynthesis, 272,274 reproductive toxicity, 220 haplophytine, 47 resistance management, 116,259,261-266 hellebore, 37 resistant insects, activity on, 115 herculin, 34 rice cultivation, 119 1-[N-(heteroaromatic-methyl)]amino- site of action, 122,214,288 ! ~methylamino-2-nitroethenes, 134 soil and seed treatment, 114,118,187,195,196 1-[N-(heteroaryl-methyl)-N-methyl]• subchronic toxicity, 216 amino-1-methylarnino-2-nitroethenes, 133 synthesis, ll3 hexahydronitroimidazopyrimidine analog of systemic activity, 186 CH-IMI, 274 toxicology, 216 N -hydroxyacylnomicotines, 32 imidacloprid analogs (see also nicotinoids, 14-hydroxypaspalinine, 52 chloronicotinyl insecticides) Austin model I (AM l), 100,102 I electronic absorption, 10 1 environmental stability, 104 azidonicotinoid (AN), 274, 281,285, fish toxicity, I 04 297

frontier orbital, 102 3-methyl-2-(nitromethyl)pyridine, 75 hydrolysis, I 00 1-[N-methyl-(3-pyridylmethyl)amino ]-2- hydrophilicity, 102,104 nitroethene, 131 lipophilicity, I 02 methylxanthines, 44 log k value on HPLC, 104 monoazacycloalkanes, 77 Mulliken charge, 102 Mospiran® (see acetamiprid), 150 oxidation, 100 myosmine, 4,5,32 partition coefficient (Pow), 102,103,104 5'-methyl-, 4,5 photolysis, I 00,10 I, I 02 myrmicarin 215A, 48 structure-activity relationship, 92-99 structure-lipophilicity relationship, I 03, I 04 N systemic property, 102, I 04 Na+ channel, 36,37,39,42 triplet excited states, 102 naphthylisoquinolines, 45 UV absorption, 101,102 neoherculin, 34 vaporization, 100 neonicotine, 32 water solubility, 10 nereistoxin, 17,33,51, 127,254 indanomycin, 5 NI-25 (see acetamiprid), 150 isoboldine, 44 nicotine, 3,6.9,10,11, 16,18, 19,21,22,29,30,31, isobutylamides, 29,33,34 32,42,45,49, I 03,120,121,223,237, isonicoteine (see 3,2'- or 2,3'-dipyridyl) 238,254,276,277,282 , 54 action, brain, hippocampus, 224 K long-term potentiation, 225 K+ channel, 33,41 septohippocami pathway, 229 kalecide, 34 action, Torpedo, 17 , 17 acylated nor-, 8~12 6-amino-. 246 L analogs, 7 6-bromo-, 246 lindane, 118 6-chloro-, 246 , 17,33,120,121 6-flu oro-, 246 6-methoxy-, 246 M 5'-methylnor-, 4,5 malathion, 52,159, nor-, 4,5,31,32 market, 109,111,119,177 resistance, 32,256 , 17,226 review, 3 methidathion, 173,174 toxicity, 15 methomyl, 138,159 nicotinic acetylcholine receptor (nAChR), methyl N-cyanoacetimidate, 156 3, 15.24,30,33,40,42,45,51, 109,120, 1-methylamino-2-nitroethenes, 133 121,122, 178,223,237,271,275,283,284 1-methylamino-1-(3-pyridylmethylamino)- affinity chromatography, 273,279,285,287 2-nitroethenes, 131 agonists, 121,122 N-methylcarbamates, 40 antagonists, 121, 122 , 120,121,230 binding, 13, 16, 19,120,122,164,165,240, N-methyl-nitroguanidine, 183 244,24 7 ,275,276, 298

biochemistry, 120 toxicological characterization, 277 brain, 223,283 translocation, 17 electrophysiological assay, 285 nicotinoyl dihydroagarofuran, 46 electrophysiology, 121.275 nicotyrine, 4,5, 16,32 expression in Xenopus oocyte dihydro-, 4,5,7,32 (see Xenopus) nor-. 4.5,32 gel electrophoresis, 280 nigragillin, 54 immunohistochemistry, 286 nitenpyram, 9,16,103, 110.111,120,121.127, insects, 17, 122,271,276,283,284,285 134,177,178,179,180,188,254,258 ion channel complex, 17 ,22,286, animal metabolism, 135 isolation, 279,286 binding, 17,120, ligands, 6, 16,120,276,277 chemical properties, 134 mammalian, 15,224,237,278,283 environmental fate, 136 photoaffinity labelling, 274,280,287,288 field performance, 138-141 radiolabeled ligands, 272 insecticidal activity, 137,138.185 structure and function joint action with cartap, 146 insects, 284 mode of action, 143,146 mammals, 274,278,280,283,287,288 nontarget organisms, effect on, 134,141 subtypes, subunits, 122,223,225,237, physical properties, 134 278,279,280,283,284,286,287 pollinators, effect on, 143 Torpedo, 17 residual activity, 132 nicotinoids, neonicotinoids, 4,9, I 0,22, 177,178,278 resurgence, 143 (see also imidacloprid-analogs structure-activity relationship, 129 chloronicotinyl insecticides) systemic action, 137,186 binding (see nAChR) time course of efficacy, 144 binding-toxicity relationship, 13,277 nithiazin(e), 9, 16, 19,20,79,80,81 ,83,85,86,91, comparative molecular field analysis, 250 92,103,110,120,121,152,177,180 definition, 10 binding, 17,19,120 essential moiety, pharmacophore, ester derivatives, 83 5, 14,23, I 05.179,239,242.249, fly trap device, 86 first-, 2nd-generation, 180 N-formyl-, 81,85 historical background, 9,91, 109,177,253 mode of action, 85 ionization, 5 nitroenamine structure, 76 mode of action, 7, II ,21, 120, 146, 164, photochemical reactivity, 83 213,214,223,237,288 prodrugs, 83 'W-NMR. 14 vapor pressure, 86 partition coefficient (Pow}, 18,102,103,104 nitroimino-oxadiazinane, 181 pKa, 5,7 2-nitroimino-1,3-pyrrolidine, 113 QSAR, 246,248 nitromethylene heterocycles (NMHs), 71,181 structural elements, 179 (see also nithiazin(e)) structure-activity relationship, chemical exploration, 75 insects, 4, 13,19,92, 129,154,178,271,277 derivatives from, 84 mammals, 237-250 discovery, 71 subclasses, 10, 180 explosion, 78,82 synthesis, 7, Ill, 128,156,183 knockdown activity, 86 299

lead compound, 71 pipercide, 36 light sensitivity, 80 10,11-dihydro-, 36 mode of action, 85 piperine, 35 nitroimino analogs, 80,81 piperlonguamine, 35 reaction with electrophilic reagents, 84 pirimicarb, 116,138,159,167,191 structure-activity relationship, 72-74 PMNI, 12,19,20 storage stability, 80 6-chloro- (nitromethylene analog of synergism, 72,75,85 imidacloprid; CH-!M[), 12,17,18,19,20 tautomerism, 76,77 6-methyl-, 12,19,20 zwitterionic characteristic, 77,79 S-analog of, 12,19 2-(nitromethylene)-1-azacycloalkanes. 87 polyzonamine, 49 nitromethylenes, 10,126,177 (see also Premisen.\ 114 (see imidacloprid) nitromethylene heterocycles) 0-propyl 0-(2-propynyl)phenylphosphonate acyclic-, 128,181 (PPP), 19,277 N-formyl-, 127 protoveratrine A,B, 39 N-pyridylmethyl-, 128 ProvadoTM, 114 (see imidacloprid) 2-(nitromethyl)pyridines, 75 psychoactive drugs, 24 2-(nitromethyl)pyridinium hydroxide, 79 pumiliotoxin 251 D, 50 2-(nitromethyl)-3,4,5,6-tetrahydropyridine, 75 pyrethrin, 45 NMHs (see nitromethylene heterocycles) "Pyrethrin", 34 nodulisporic acid A, 54 pyrethroids, 36,37 nominine, 52 3-pyridylmethylamines (aminomethylpyridine, Non Pest Strip®, 86 AMP), 5,6,8,22,240 noranabasamine, 50 1-(3-pyridylmethylamino)-2-nitroethenes, 129 pyrrol, 52 0 pyrrolomycin C, 52 octopamine, 43 okaramine B, 54 Q oxadiazinane, 183 Quickstrike®, 87 (see nithiazine) oxidative phosphorylation, quinuclidinyl benzilate, 276 uncoupler, 52 R p resistance (see also cross-resistance) paraherquamide, 54 chloronicotinyls, 258 parathion (parathion-ethyl), 72, 116 genetic consideration, 255 PCP (see phencyclidine) management, 253,259 pellitorine, 34,35 ritigalin, 37 permethrin, 36.52,171 rocaglamide, 43 phosphodiesterase inhibition, 44 rotenone, 52 photoaffinity labeling, 280 ryania, 40 physostigmine (eserine), 39,40,44,54 ryanodine, 40 AChE inhibition, 39,40 ryanodol, 40 binding to nAChR, 40 ryanoids, 40 fi-picoline, 112 300

s N-[ 1-(2-thienyl)cyclohexyl]piperidine (TCP), 17 thiocyclam, 254.255 sabadilla, 3 7 thioimidate-type ester intermediates, 82 sanshool-1, 34 basicity and reactivity, 82 sclerotiamide, 52 TI-435, 179, 180,181 SO-compounds (see nitromethylene hetero- TMA (tetramethylammonium). 15.16 cycles) actomatine, 39 sesamex, 72 trimethaphan, 17 a-solanine, 3<; tuberstemonine, 46 sparteine, 33 d-tubocurarine (d-TC), 17.120,121,276,282 spilanthol, 34 spinosyn, 123 stemofoline, 46 u structure-activity relationship (see each group) unsaturated amides, 34 acetamiprid, acyclic nitroethene, binding study, 37 dioncophylline, imidacloprid analogs, mode of action. 34,37 neonicotinoids, nicotinoids, nitenpyram structure-activity relationship, 36 analogs, nitromethylene heterocycles, ryanoids, unsaturated amides, v Veratrum alkaloids 3-0-vanilloylveracevine. 38 structure-lipophilicity relationship, Vapona insecticide®, 86 imidacloprid analogs. 103,104 veracevine, 38 strychnine, 120,121 veratridine, 37,50 sulprofos, 170 vinyl phosphates, 72 synergism, synergist, 19,34,36,72,277

T w wilfordine, 46 TCP (see N-[1-(2-thienyl)cyclohexyl] wilforine, 46 piperidine) teflubenzuron, 167 tetrahydroanacyclin, 34 X theophylline, 44 Xenopus oocyte, 15, 278,284,285,286 thiamethoxam, 182 xenorhabdins, 52 thianicotinyls, 180,182