••
Pyrazoline-type insecticides (PTIs) are potent
neurotoxicants that cause cessation of feeding,
abnormal movement, and paralysis in arthropods.
Indoxacarb, the first insecticide
in this class to achieve commercial registration,
is a proinsecticide that is selectively activated in insects
to form the insecticidal N-decarbomethoxyllated metabolite,
DCJW is another pyrazoline-type compound that is an effective
insecticide but was not registered for use due to its
unacceptable mammalian toxicity ([Meier et al., 1992],
[Silver and Soderlund, 2005a] and [Silver and Soderlund,
2005b]).
Ref: Silver KS, Soderlund DM (2007).
Point mutations at the local anesthetic receptor site
modulate the state-dependent block of rat Nav1.4 sodium
channels by pyrazoline-type insecticides. NeuroToxicology
28:3 655-663. (Available at ScienceDirect.)
••
See also: Action of pyrazoline-type insecticides
at neuronal target sites. Silver
KS, Soderlund DM (2007). Pesticide Biochemistry and Physiology
81:2 136-143. (Available at ScienceDirect.)
|
Biological Control - Volume 34, Issue 1 , July 2005,
Pages 108-114
Effects of spinosad and indoxacarb on
survival, development, and reproduction of the multicolored Asian
lady beetle (Coleoptera: Coccinellidae)
T.L. Galvan, , R.L. Koch and W.D. Hutchison
Department of Entomology, 219 Hodson Hall, 1980 Folwell Avenue,
University of Minnesota, St. Paul, Minnesota, 55108, USA
Use of selective insecticides, such as spinosad and indoxacarb,
that are more toxic to lepidopteran pests than to Harmonia axyridis
(Pallas), could facilitate conservation of this predator in sweet
corn integrated pest management (IPM). We examined the effects
of spinosad and indoxacarb on survival, development, and reproduction
of H. axyridis by spraying first instars and adult females. Treatments
for the first instar assay were spinosad at 10, 25, and 50% of
the field rate (FR), indoxacarb at 10% FR, and water (untreated
check). We recorded survival of each life stage, developmental
time to adults, and adult weight. Treatments for the adult female
assay were spinosad at 50 and 100% FR, indoxacarb at 50% FR, and
water (control). Each day, we recorded female survival and reproductive
capacity. Indoxacarb decreased survival of first instars and adults,
extended the developmental time for first instars to become adults,
and reduced the fecundity of H. axyridis females. Spinosad decreased
survival of first instars, extended the time for first instars
to become adults, decreased weight gain, and reduced the fertility
of H. axyridis females. Our results suggest that spinosad and
indoxacarb may reduce H. axyridis population growth by affecting
its survival, development, and reproduction. We also conclude
that indoxacarb, when applied at 10% FR, has more lethal and sublethal
effects on H. axyridis than spinosad applied at 10, 25 or 50%
FR. The importance of sublethal effects of insecticides, as well
as acute toxicity, in toxicological studies with natural enemies
is discussed within the context of biological control and IPM.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15481830
Pest Manag Sci. 2004 Oct;60(10):1025-34.
Integrated pest management approach for
a new pest, Lacanobia subjuncta (Lepidoptera: Noctuidae), in Washington
apple orchards.
Doerr MD, Brunner JF, Schrader LE.
Department of Entomology, Washington State University, Tree Fruit
Research and Extension Center, Wenatchee, WA 98801, USA. mdoerr@wsu.edu
Bioassays of Lacanobia subjuncta (Grote and Robinson) larvae
established baseline LC50 values and identified
the potential of reduced-risk, organophosphate replacement and
naturally derived insecticides (eg chloronicotinyls, spinosyns,
oxadiazines, insect growth regulators, microbial insecticides
and particle films) to control this pest. The toxicities of these
products were compared with those of organophosphate, carbamate,
chlorinated cyclodiene and synthetic pyrethroid insecticides used
in the management of lepidopteran pests in Washington apple orchards.
Field trials were conducted comparing candidate insecticides to
conventional alternatives. Several new insecticides (eg spinosad,
methoxyfenozide, indoxacarb and an
aluminosilicate particle film) proved to be effective for the
management of L subjuncta. We summarize the goals and challenges
of developing an integrated pest management program for new and
resurgent pests as insecticide tools continue to change, and propose
a hypothesis for the sudden increase in pest status of L subjuncta
based on organophosphate tolerances. The role of novel insecticides
with unique modes of action in resistance management and the encouragement
of biological control are also discussed.
PMID: 15481830 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12974351
Pest Manag Sci. 2003 Sep;59(9):999-1006.
Modulation of sodium channels by the oxadiazine insecticide indoxacarb
and its N-decarbomethoxylated metabolite in rat dorsal root ganglion
neurons.
Tsurubuchi Y, Kono Y.
Institute of Agriculture and Forestry, University of Tsukuba,
Tsukuba 305-8572, Japan. tsurubuchi@yakubutu.co.jp
The effects of the oxadiazine insecticide
indoxacarb and its N-decarbomethoxylated
metabolite (DCJW) on tetrodotoxin-resistant (TTX-R)
voltage-gated sodium channels in rat dorsal ganglion neurons were
studied using the whole-cell patch clamp technique.
Indoxacarb and DCJW suppressed the peak amplitude of action potentials,
and DCJW exhibited a faster time course
and higher potency than indoxacarb in the blocking effects.
In voltage-clamp experiments, indoxacarb
and DCJW suppressed TTX-R sodium
currents in a time-dependent manner without a steady-state
level of suppression. IC50 values for indoxacarb and DCJW on TTX-R
sodium currents were estimated to be 10.7 and 0.8 microM after
25 min of bath application, respectively. DCJW was about 10 times
more potent than indoxacarb in blocking TTX-R sodium currents.
Although the suppressive effects of indoxacarb
were partially reversible after washout with drug-free external
solution, no recovery of sodium current
was observed in DCJW treated neurons after prolonged washout.
In current-voltage relationships, both
indoxacarb and DCJW blocked the sodium
currents to the same degree in the entire range of membrane potentials.
The sodium conductance-voltage curve was not shifted along
the voltage axis by indoxacarb and DCJW at 10 microM. In contrast,
the steady-state inactivation curves were shifted in the hyperpolarizing
direction by indoxacarb as well as by DCJW. Based on these results,
it was concluded that indoxacarb and DCJW potently blocked the
TTX-R sodium channel in rat DRG neurons with hyperpolarizing shifts
of the steady-state inactivation curves, suggesting preferential
association of the insecticides to the inactivated state of sodium
channels. The small structural variation
between indoxacarb and DCJW resulted in clear differences in potency
for blocking sodium channels and reversibility after washout.
PMID: 12974351 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12564385&dopt=Abstract
Neurotoxicology.
2003 Jan;24(1):83-96.
Voltage-dependent
block of sodium channels in mammalian neurons by the oxadiazine
insecticide indoxacarb and its metabolite DCJW.
Zhao
X, Ikeda T, Yeh JZ, Narahashi T.
Department
of Molecular Pharmacology and Biological Chemistry, Northwestern
University Medical School, 303 East Chicago Avenue, Chicago, IL
60611, USA.
Indoxacarb
is a newly developed insecticide with high insecticidal activity
and low toxicity to non-target organisms. Its metabolite, DCJW,
is known to block compound action potentials in insect nerves
and to inhibit sodium currents in cultured insect neurons. However,
little is known about the effects of these compounds on the sodium
channels of mammalian neurons. We compared the effects of indoxacarb
and DCJW on tetrodotoxin-sensitive (TTX-S) and tetrodotoxin-resistant
(TTX-R) sodium channels in rat dorsal root ganglion neurons by
using the whole-cell patch clamp technique. Indoxacarb and DCJW
at 1-10 microM slowly and irreversibly blocked both TTX-S and
TTX-R sodium channels in a voltage-dependent manner. The sodium
channel activation kinetics were not significantly modified by
1 microM indoxacarb or 1 microM DCJW. The steady-state fast and
slow inactivation curves were shifted in the hyperpolarization
direction by 1 microM indoxacarb or 1 microM DCJW indicating a
higher affinity of the inactivated sodium channels for these insecticides.
These shifts resulted in an enhanced block at more depolarized
potentials, thus explaining voltage-dependent block, and an apparent
difference in the sensitivity of TTX-R and TTX-S channels to indoxacarb
and DCJW near the resting potential. Indoxacarb
and its metabolite DCJW cause toxicity through their action on
the sodium channels.
PMID: 12564385
[PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12370061&dopt=Abstract
Mini Rev Med
Chem. 2002 Aug;2(4):419-32.
Nerve membrane
ion channels as the target site of insecticides.
Narahashi
T.
Department
of Molecular Pharmacology and Biological Chemistry, Northwestern
University Medical School, Chicago, IL 60611, USA. tna597@nwu.edu
Most insecticides
are potent neurotoxicants that act on various neuroreceptors and
ion channels. However, the major target receptors are limited
to sodium channels, GABA receptors, and nicotinic acetylcholine
receptors. DDT and pyrethroids act similarly on sodium channels
to keep them open leading to hyperexcitation. Indoxacarb
inhibits sodium channels and certain subtypes of nicotinic receptors.
Dieldrin, lindane and fipronil block GABA receptors. Imidacloprid
modulates nicotinic receptors in a complex manner. Spinosad's
major target site appears to be nicotinic receptors.
Publication
Types: Review; Review, Tutorial
PMID: 12370061
[PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12192909&dopt=Abstract
Pest Manag
Sci. 2002 Aug;58(8):834-8.
Broad-spectrum
insecticide resistance in obliquebanded leafroller Choristoneura
rosaceana (Lepidoptera: Tortricidae) from Michigan.
Ahmad
M, Hollingworth RM, Wise JC.
Department
of Entomology, Center for Integrated Plant Systems, Michigan State
University, East Lansing, MI 48824, USA.
Nineteen insecticides,
belonging to nine chemical classes, were bioassayed by dietary
exposure against two strains of obliquebanded leafroller, Choristoneura
rosaceana, collected from Michigan apple orchards. Berrien is
a putatively organophosphate-resistant strain from a commercial
orchard with a history of insecticide use, and Kalamazoo a susceptible
strain from an isolated and unsprayed orchard. The Berrien strain
was moderately resistant (about 25-fold) to organophosphates such
as azinphos-methyl and chlorpyrifos. Very low resistance (< 10-fold)
was also observed to pyrethroids such as cypermethrin, zeta-cypermethrin,
bifenthrin, deltamethrin and esfenvalerate, to the ecdysone agonists
tebufenozide and methoxyfenozide, and to the chlorinated pyrrole
chlorfenapyr. Endosulfan and carbamates such as thiodicarb, methomyl
and carbaryl had low intrinsic toxicities against both strains,
with little difference in sensitivity between them. There was
no resistance to spinosad. Emamectin benzoate was found to be
the most toxic insecticide against C rosaceana, with slightly
higher lethal doses required for the Berrien strain. Unexpectedly,
Berrien exhibited a very high level of resistance (> 700-fold)
to indoxacarb, which has never been used in Michigan to control
this insect pest. The active metabolite of indoxacarb, DCJW, was
considerably more toxic than the parent compound, but the resistance
against DCJW was comparable to that seen with indoxacarb.
This indicates that a failure to activate indoxacarb was not the
mechanism of resistance in Berrien. The low level of resistance
to several chemistries recorded in Michigan C rosaceana can be
managed at this stage by adopting a rotation of chemistries having
different modes of action.
PMID: 12192909
[PubMed - in process]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12216826&dopt=Abstract
J Econ Entomol.
2002 Aug;95(4):820-5.
Resistance
and cross-resistance to four insecticides in populations of obliquebanded
leafroller (Lepidoptera: Tortricidae).
Smirle
MJ, Lowery DT, Zurowski CL.
Agriculture
and Agri-Food Canada, Pacific Agri-Food Research Centre, Summerland,
BC, Canada. smirlem@em.agr.ca
Populations
of obliquebanded leafroller, Choristoneura rosaceana (Harris),
were collected from organic and conventionally managed orchards
located in the Okanagan and Similkameen Valleys of British Columbia.
Neonate F1 progeny were assayed for resistance to azinphosmethyl,
tebufenozide, methoxyfenozide, and indoxacarb using a leaf disk
bioassay. Significant differences in resistance levels among populations
were observed for all four insecticides. Insects collected from
organic sites were more susceptible to all insecticides than were
insects collected from conventional sites. Resistance to the benzoylhydrazine
insect growth regulators tebufenozide and methoxyfenozide was
highly correlated with resistance to azinphosmethyl across populations,
indicating cross-resistance between these compounds. The
highest levels of resistance were observed with indoxacarb,
but resistance levels to indoxacarb did not correlate with those
for azinphosmethyl. Dose-response regression lines for tebufenozide
were parallel across populations, suggesting that the resistance
mechanism(s) were quantitatively, but not qualitatively, different.
Cross-resistance between azinphosmethyl and benzoylhydrazine insecticides
indicates that a resistance management strategy for obliquebanded
leafroller involving the rotation of these materials is not likely
to be successful.
PMID: 12216826
[PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11455646&dopt=Abstract
Pest Manag
Sci. 2001 Feb;57(2):153-64.
The discovery
of indoxacarb: oxadiazines as a new class of pyrazoline-type insecticides.
McCann
SF, Annis GD, Shapiro R, Piotrowski DW, Lahm GP, Long JK, Lee
KC, Hughes MM, Myers BJ, Griswold SM, Reeves BM, March RW, Sharpe
PL, Lowder P, Barnette WE, Wing KD.
DuPont
Crop Protection Products,
Stine-Haskell Research Center, PO Box 30, Newark, DE 19714, USA.
stephen.f.mccann@usa.dupont.com
The evolution
of the insecticidal pyrazoline moiety that was originally
discovered in 1972 has led to the discovery of a new crop
insecticide, indoxacarb, which is the first
commercialized pyrazoline-type sodium-channel blocker.
Both monocyclic and fused-tricyclic pyrazolines and pyridazines,
as well as structurally related semicarbazones were examined prior
to the discovery of analogous tricyclic oxadiazines which had
similarly high activity as well as favorable environmental dissipation
rates and low toxicity to non-target organisms. The eventual leading
candidate, DPX-JW062, was originally
obtained as a racemic molecule, but a chiral synthesis was developed
which produces material that is 50% ee in the insecticidal (+)-S-enantiomer
(DPX-MP062, indoxacarb).
PMID: 11455646
[PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11159709&dopt=Abstract
Br J Pharmacol.
2001 Jan;132(2):587-95.
Indoxacarb,
an oxadiazine insecticide, blocks insect neuronal sodium channels.
Lapied
B, Grolleau F, Sattelle DB.
Laboratoire
de Neurophysiologie, UPRES EA 2647-RCIM, Universite d'Angers,
UFR Sciences, 2 Bd Lavoisier, F-49045 Angers cedex, France. bruno.lapied@univ-angers.fr
1. Decarbomethoxyllated
JW062 (DCJW), the active component of a new oxadiazine insecticide
DPX-JW062 (Indoxacarb), was tested on action potentials and the
inward sodium current recorded from short-term cultured dorsal
unpaired median neurones of the cockroach Periplaneta americana.
2. Under whole-cell current-clamp conditions, 100 nM DCJW reduced
the amplitude of action potentials and induced a large hyperpolarization
of the resting membrane potential associated with a 41% increase
in input resistance.
3. In voltage-clamp, DCJW resulted in a dose-dependent inhibition
(IC(50) 28 nM) of the peak sodium current. Based on IC(50) values,
the effect of DCJW was about 10 fold less potent than tetrodotoxin
(TTX) but 1000 fold more potent than the local anaesthetic lidocaine.
DCJW (100 nM) was without effect on activation properties of the
sodium current, reversal potential, voltage dependence of sodium
conductance and on both fast and slow steady-state inactivations.
4. TTX (2 nM) resulted in 48% inhibition of the peak inward sodium
current. Co-application of TTX (2 nM) with various concentrations
of DCJW produced an additional inhibition of the peak inward current,
indicating that the blocking actions of DCJW and TTX were distinct.
Co-application of lidocaine (IC(50) 30 microM) with various concentrations
of DCJW produced a reduction of the apparent potency of DCJW,
suggesting that DCJW and lidocaine acted at the same site.
5. DCJW (100 nM) did not affect inward calcium or outward potassium
currents.
6. This study describes, for the first time, the action on insect
neuronal voltage-dependent sodium channels of Indoxacarb, a new
class of insecticides.
PMID: 11159709
[PubMed - indexed for MEDLINE]
From Toxline at Toxnet
Source: 218TH NATIONAL MEETING OF THE AMERICAN CHEMICAL SOCIETY,
PARTS 1 AND 2, NEW ORLEANS, LOUISIANA, USA, AUGUST 22-26, 1999.YABSTRACTS
OF PAPERS AMERICAN CHEMICAL SOCIETY; 218 (1-2). 1999.
AGRO 42. Field studies using radiolabeled test substances: Outdoor
metabolism or field dissipation?
Environmental Fate,
DuPont Agricultural Products, Experimental Station, Wilmington,
DE, USA.
BAREFOOT AC. RUHL JC
BIOSIS COPYRIGHT: BIOL ABS. RRM FIELD STUDIES USING RADIOLABELED
TEST SUBSTANCES: OUTDOOR METABOLISM OR FIELD DISSIPATION&YMEETING
ABSTRACT PESTICIDES POLLUTION TOXICOLOGY ENVIRONMENTAL CONTAMINATION
INDOXACARB PESTICIDE CARBON-14 LABELED
OUTDOOR METABOLISM FIELD DISSIPATION METSULFURON METHYL ENVIRONMENTAL
MONITORING
Keywords:
General Biology-Symposia
Radiation-General
Ecology
Biochemical Studies-General
Biophysics-General Biophysical Studies
Toxicology-Environmental and Industrial Toxicology
Public Health: Environmental Health-Air
Pest Control
CAS Registry Numbers:
173584-44-6
173584-44-6
74223-64-6
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10499355
Neurotoxicology.
1999 Aug;20(4):561-70.
Effects
of the oxadiazine insecticide indoxacarb, DPX-MP062, on neuronal
nicotinic acetylcholine receptors in mammalian neurons.
Zhao
X, Nagata K, Marszalec W, Yeh JZ, Narahashi T.
Department
of Molecular Pharmacology and Biological Chemistry, Northwestern
University Medical School, Chicago, IL 60611, USA.
The effects
of the novel oxadiazine insecticide DPX-MP062
and its metabolite (DCJW) on neuronal
nicotinic acetylcholine receptors (AChRs) were investigated using
the whole-cell patch clamp technique in rat embryonic cerebral
cortical neurons in primary culture. DPX-MP062, applied at concentrations
of 1 and 10 microM to the bath, reduced the peak amplitude of
ACh-induced, rapidly decaying currents to 46.8+/-8.8% (n=9) and
15.7+/-5.0% (n=4) of the control, respectively. The effect was
irreversible after washing with drug-free solution. DCJW at either
1 microM or 10 microM had similar actions but the potency was
much less than that of DPX-MP062. The slowly desensitizing currents
induced by low concentrations of ACh (0.1-10 microM) were augmented
and those induced by high concentrations of ACh (100-1000 microM)
were inhibited by 10 microM DPX-MP062 with great acceleration
of the current decay in a time-dependent manner. These effects
were use independent and reversible after washing with drug-free
solution. In contrast, DCJW at 10 microM did not show significant
effects on peak amplitude and decay phase of the slowly desensitizing
ACh-induced current in cortical neurons. These
results indicate that the oxadiazine insecticide DPX-MP062 has
potent modulating actions on neuronal nicotinic AChRs. The neuronal
nicotinic AChR could be one of the primary target sites of the
insecticide in mammals.
PMID: 10499355
[PubMed - indexed for MEDLINE]
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