Insect Control: Biological and Synthetic Agents - Index of

2 Indoxacarb and the Sodium Channel Blocker
Insecticides: Chemistry, Physiology, and Biology
in Insects
K D Wing, J T Andaloro, and S F McCann,
E. I. Du Pont de Nemours and Co., StineHaskell
Research Laboratories, Newark, DE, USA
V L Salgado, Bayer CropScience AG, Monheim am
Rhein, Germany
ß 2010, 2005 Elsevier B.V. All Rights Reserved
2.1. Introduction 35
2.2. Chemistry of the Na + Channel Blockers 36
2.2.1. Chemical Evolution and Structure–Activity of the Na + Channel Blocker Insecticides 36
2.2.2. Chemistry and Properties of Indoxacarb 36
2.3. Metabolism and Bioavailability of Indoxacarb 37
2.3.1. Bioactivation of Indoxacarb 37
2.3.2. Catabolism of Indoxacarb and Other Na + Channel Blocker Insecticides 39
2.4. Physiology and Biochemistry of the Na + Channel Blockers 39
2.4.1. Symptoms of SCBI Poisoning in Insects: Pseudoparalysis 39
2.4.2. Block of Spontaneous Activity in the Nervous System 40
2.4.3. Block of Na + Channels in Sensory Neurons 41
2.4.4. Mechanism of Na + Channel Block 42
2.4.5. SCBIs Act at Site 10 on the Na + Channel 45
2.4.6. The Molecular Nature of Site 10 in Insects 46
2.4.7. Biochemical Measurements of the Effects of SCBIs 47
2.4.8. Intrinsic Activity of Indoxacarb on Na + Channels 48
2.4.9. Effects of SCBIs on Alternative Target Sites 49
2.5. Biological Potency of Indoxacarb 50
2.5.1. Spectrum and Potency of Indoxacarb in the Laboratory 50
2.5.2. Safety of Indoxacarb to Beneficial Insects 51
2.5.3. Sublethal Effects of Indoxacarb 51
2.5.4. Spectrum and Insecticidal Potency of Indoxacarb in the Field 51
2.5.5. Indoxacarb and Insecticide Resistance 52
2.6. Conclusions 53
2.1. Introduction
There is an increasing need to discover novel chemical
insecticides which act on unique biochemical
target sites. This is necessary for insecticide resistance
management, to maintain agricultural food
and fiber production at reasonable economic levels,
and also to retain the effectiveness of older and new
classes of chemistry as useful tools.
The modes of action of the major insecticide classes
are reviewed in Ishaaya (2001) and in this Encyclopedia.
These insecticidal compounds are required
not only for economic pest control, but also as
critical probes to elucidate their respective biochemical
target sites, allowing insights into their
fundamental biological function.
While there is an increasing need for new agrochemicals,
regulatory requirements for the registration
of new insecticides continue to escalate, and society’s
requirements for safety to nontarget organisms
and the environment and compatibility with ongoing
agricultural practice, pose increasing challenges.
The voltage-gated sodium (Na þ ) channel is a primary
insecticide target for the synthetic and natural
pyrethroids, DDT, N-alkylamides, and a host of
natural product and peptide toxins (Zlotkin, 2001).
At least ten independent target sites exist for
these compounds, based on functional studies, and
the compounds can exert allosteric effects on one
another via these independent sites. In addition, it
has been definitively shown that specific genetic mutations
in the Na þ channel in both laboratory and
field insects can confer resistance to pyrethroids and
DDT (see Chapter 1). The discovery of additional
new Na þ channel toxins acting at novel sites thus