Insecticides are essential tools
for preventing or minimizing insect damage to, and significantly increasing the
quality and quantity of crops, as well as for improving the quality of life for
humans, domestic animals and livestock. There are currently more than 20
different mechanisms, or modes of action. by which various commercial insecticides
control insects by disrupting specific vital biological processes, but not all of these can be used
against any particular pest insect. Mode
of action diversity is the most important tool we have for ensuring our
sustained ability to control insect pests. Repeated application of insecticides
with the same mode of action contributes to resistance by killing the
susceptible insects and leaving those with resistance to that entire class of
insecticides. Insects are animals, with similarities to and differences from
other animals. Indeed, all living things share a common set of biological
processes that make life possible, and the more closely related two organisms
are, the more vital processes they have in common. Ideally, insecticides would
specifically target vital processes unique to pest species, but that is seldom
possible. Some insecticides target processes unique to insects and
closely-related arthropods, such as the biosynthesis of chitin, a tough semitransparent
polysaccharide that is the main component of the insect’s exoskeleton. Key insecticide target groups include are:
neuromuscular poisons, respiratory poisons, gut disruptors and insect growth
regulators .
Vital processes in organisms are carried out largely by
proteins – macromolecules composed of chains of amino acids that occur in many
different forms and are the workhorses of the body . Proteins in the body are
not structural, but are intricate molecular machines that occur in minute
quantities – sometimes just a few molecules per cell – and perform various
essential functions. Many of these non-structural proteins are: 1) enzymes that
catalyze biochemical reactions, 2) receptors that transduce signals, or 3)
channels and other types of transport proteins, which help substances cross
cell membranes. Because of their complexity and the key functions they carry
out, enzymes, receptors and channel proteins are often affected by drugs,
toxins or insecticides.
THE CHALLENGE.
The challenge of controlling pests
with insecticides is that the more similar two organisms are, the more similar
their proteins are as well. This in turn increases the challenge to develop low
risk and selective products. For example, the natural insecticide nicotine
mimics the action of the endogenous
(substance that originates within an organism, tissue or cell) chemical
messenger acetylcholine (ACh) in the insect nervous system, and has the same
action in humans. Nicotine, though natural, is much more toxic to humans than
any commercial insecticide. The nicotine contained in 30 - 40 cigarettes can be
lethal to an adult when administered as
a single dose
TARGET SITE.
The location on
/or within a particular protein where a toxicant binds and exerts its toxic action is
known as the target site, and the
interactions of the toxicant with that site define the toxicant’s mode of
action.
CLASSIFICATION OF INSECTICIDE
Compounds of
widely different chemical structure can bind at the same target site and have
exactly the same mode of action. Heritable changes that hamper action at the
target site can confer resistance to entire classes of insecticides. The
Insecticide Resistance Action Committee (IRAC) is a specialist technical group
of the industry association CropLife, organized to provide a coordinated
industry response to prevent or delay the development of resistance in insect
and mite pests. IRAC classifies insecticides into groups with a common mode of
action and then into chemical subgroups within those group. The four categories are: neuromuscular
toxins ( which attack the nervous system or muscles), insect growth regulators
(IGRs)( which affect growth and development) , respiratory
poisons( also called metabolic poisons, which affect energy metabolism) and gut disruptors,( which destroy the
integrity of the gut lining). In addition to these four categories, there is a
group of compounds that are thought to be non-specific multi-site inhibitors,
which interact with one or more specific target sites.
PROPERTIESS OF INSECTICIDES
·
Speed of action
·
spectrum
of control
·
Environmental
safety, are characteristic of their mode of action.
Neuromuscular disruptors and respiratory disruptors directly affect the
coordination and energy state, respectively, so they are usually rapid and
broad in spectrum of activity, controlling a wide variety of pests.
ADME
Absorption,
Distribution, Metabolism and Excretion In order for an insecticide to act at
its target site, it must enter the insect through one or more absorption
routes, including
·
Absorption through the cuticle
·
Orally through the consumption of treated foliage or sap,
·
Inhalation through the spiracles as a vapor.
Once absorbed into the body, the active
ingredient then distributes throughout the body to reach the target sites,
which may only occur deep within certain tissues. At the same time, natural
defense mechanisms of the insect are acting to break down and excrete the
insecticide molecules. These processes, which together with mode of action
determine the biological effect of the insecticide, are absorption,
distribution, metabolism and excretion, respectively.
TYPES OF INSECTICIDES.
3
types,
·
Non-lethal chemicals, eg:repellant,hormone
mimics, growth regulator,anorestic agent
among other.
·
Chemicals that cause physical problems, eg:
sufactants,sticky substance, desiccant
·
Chemicals that act as barrier, eg: oil film on
the surface of water against mosquito larvae.
Insecticides
can also be grouped into chemical families. Namely;
·
ORGANOCHLORIDES: It’s an organic compound that
contain at least one covalently bonded chlorine atom. Eg; DDT, dicofol,heptachlor,.
And its target is the sodium channel.
·
PYRETHRIOD: Synthetic chemical compound
pyrethrins which are produce by flowers of pyrethrums. They act on the sodium
channels causing paralysis.
Examples
includes: Allethrin,(raid),Befenthrin,permenthrin.etc
·
CABAMATES: Compouds derived from carbamic acid
{NH2COOH}. Carbamate group,carbamate easter. Examples are:aldicabs,carbofuran.
·
ORGANOPHOSPHATES: They are generally easter of
phosphoric acid. They are the insecticides which act on the acetylcholinesterase.
Examples are: parathion,malatrhion,diazinon etc.
MODE OF ACTION.
According to
IRAC mode of insectides action can be grouped into
·
Group 1: Acetyl
cholinesterase (AChE) Inhibitors; Acetyl cholinesterase (AChE), a critical
enzyme in the function of the insect central nervous system, is the target of
inhibition by organophosphate (OP)
and Carbamates insecticides.
·
Group 1A:
Carbamates:
The
insecticidal activity of carbamates was first discovered in 1947 at the Geigy
Company in Switzerland, but it wasn’t until 1956 that carbaryl, the first
successful carbamate insecticide, was
introduced by Union Carbide. Since then, BASF, DuPont, FMC Corporation, Syngenta, Dow AgroSciences,
Bayer and other companies have developed and commercialized their own
proprietary Carbamates insecticides. Carbamates are mostly broad spectrum
insecticides used on cotton, fruit, vegetables,
row and fodder crops. Examples of Carbamates Insecticides Common name carbaryl, carbosulfan , Marshal.
Group 1B: Organophosphates :Notable
members of the group include Perfekthion insecticide (dimethoate)
Mode of Action: Acetyl cholinesterase
inhibitors bind to and inhibit the enzyme that’s normally responsible for
breaking down AChE after it has carried
its message across the synapse. This allows the ACh to continue stimulating the
postsynaptic neuron, leading to overstimulation of the nervous system and
eventual death of the insect. AChE is a type of hydrolytic enzyme known as a
serine esterase, so called because of the presence of the amino acid serine
(Ser200) in the active site, whose hydroxyl side chain becomes esterified
(ester group added to molecule) by the substrate during catalysis. The acetyl
enzyme intermediate forms rapidly, and releases the acetate group with a
half-life of microseconds. Carbamates and organophospates are suicide
inhibitors of AChE. They enter the active site of the enzyme and react with the
catalytic serine residue, but the carbamoylated and phosphorylated enzymes are
much more stable than the acetylated form, so the enzyme is inhibited. Resistance to AChE inhibitors is often due
to enhanced metabolism, but modified AChE also often plays a role in many
cases. Symptoms of acute poisoning by organophosphates and carbamates can
develop within minutes to hours, depending on the route of exposure. Early
symptoms include headache, nausea, dizziness, pupillary constriction and hyper
secretion (sweating, salivation, watery eyes, and runny nose). The primary
cause of death in organophosphate poisoning is respiratory failure.
A.
ACh + AChE (Acetyl enzyme intermediate (t1/2 = microseconds) -rapid
B.
Carbamate + AChE (Carbamoyl enzyme intermediate (t1/2 ~ 15 to 20 min)-slow
C.
Organophosphate + AChE (Phosphoryl enzyme intermediate (t1/2 ~ hours or
days)-slow
Group
2: GABA-Gated Chloride Channel Antagonists
Group 2A:
Cyclodiene Organochlorines Cyclodienes:
Examples:endosulfan ,Thiodan etc.
Group 2B: Phenylpyrazoles Phenylpyrazoles are a
family of GABA-gated chloride channel
antagonists.
Mode of Action: As mentioned in the
section “Excitatory, Inhibitory and Modulatory Neurotransmission,”
gamma-aminobutyric acid (GABA) is an inhibitory
neurotransmitter used to transmit signals that inhibit the activity of
postsynaptic cells. A certain amount of
inhibition in the nervous system is essential for normal function, and blocking of the GABA-gated chloride
channels by cyclodienes and phenylpyrazoles leads to overstimulation and
convulsions. Blockers interfere with
inhibitory neurotransmission by occluding the
cchloride channel pore. In addition to GABA receptors, insects and
some other invertebrates also have
glutamate-gated chloride channels that
may play a role in inhibitory neurotransmission. Unlike other GABA-gated
chloride channel antagonists, which are
specific for GABA-gated chloride
channels, fipronil also potently blocks two types of
glutamate-gated chloride channels. This
unique multi-target mode of action may reduce
the potential for resistance development.
IRAC Group 3: Sodium Channel Modulators :
Group 3A: Pyrethroids: Pyrethrins are the insecticidal compounds
that occur naturally in this material. Synthetic analogs of pyrethrins, called
pyrethroids. Pyrethroids have been specifically designed to be more
environmentally stable than Pyrethrins, whose activity is measured in hours.
They provide long-lasting control and
improved mammalian safety relative to other products in use at the time
they were developed. These compounds are
generally effective against caterpillars, beetles, certain aphids and mites in
crops, and are used for mosquito, termite and cockroach control in non-crop
segments. In addition, certain members of the class are used to control ecto-parasites on pets and humans. Key
applications include foliar sprays in vegetable crops, oilseed rape and cotton,
as well as soil and foliar uses in maize. Examples of Pyrethroid and Pyrethrin
Insecticides:
Group
3B: DDT and methoxychlor;
Mode of Action : Sodium channel
modulators are neurotoxins that act on the action potential sodium channel.
They slow the closing and inactivation of the channel, causing it to remain
open longer than normal, which has the effect of prolonging the action
potential, When the action potential is
not promptly terminated, it can re-excite the same area of membrane, leading to
repetitive firing.
Because nerve
axons occur throughout the insect’s body, even near the surface of the cuticle
in sensory organs and motor nerve terminals, pyrethroids and DDT cause symptoms
as soon as they enter the body and are considered extremely fast-acting,
causing immediate “knockdown”
IRAC Group 4: Nicotinic Acetylcholine
Receptor (nAChR) Agonists
Group 4A: Neonicotinoids Neonicotinoids
provide excellent acute and residual control of sucking insects, including
aphids, leafhoppers, planthoppers and whiteflies, as well as certain chewing
insects including Colorado potato
beetle, rice water weevil and codling moth.
Group 4B: Nicotine :Nicotine is a
natural insecticide, made by plants (e.g., tobacco). Nicotine-based
insecticides have been banned by the EPA since 2001 because of their high acute
toxicity.
Group 4C: Sulfoxaflor
Mode of
Action : Group 4 insecticides act as agonists of acetylcholine receptors,
meaning that they mimic the action of the neurotransmitter acetylcholine (ACh).
key areas on the receptor that interact
with certain parts of the molecules
(ellipses). The cationic site is the best understood, containing a tryptophan
residue that attracts the charged nitrogen atom in ACh and nicotine.
The corresponding nitrogen atom in
imidacloprid and the sulfur atom of sulfoxaflor carry a partial positive charge
that also binds to this tryptophan residue in the insect nAChR but does not
bind very well to mammalian nAChRs. The insect receptors also contain groups
shown by the ellipse on the right, that
bind the cyano group of sulfoxaflor and the nitro group of imidacloprid, contributing further to the
insect selectivity of these molecules.
II.
Insect Growth Regulators
Insect growth regulators
(IGRs) used by the pest management industry include the juvenile hormone analogs and the chitin synthesis inhibitors. IGRs do not act on the nervous system.
They are insecticides that disrupt critical physiological functions associated
with normal insect growth, development and reproduction (egg production). IGRs
are typically not acutely (immediately) toxic to adult insects. Adult insects
exposed to IGRs usually suffer no adverse consequences, and typically live a
normal lifespan. Because they target unique biochemical pathways found only in
insects and related arthropods, IGR-containing products generally have low
mammalian toxicity . For example, the developmental physiology of many aquatic
invertebrates is similar to that of insects. Because of this, aquatic
arthropods are susceptible to some IGRs. During the life of an immature insect,
the quantity of juvenile hormone in the insect's blood is relatively high. When
present, immature insects are prevented from maturing because juvenile hormone
prevents them from developing toward adulthood. As immature insects progress
through their life cycle, however, the level of juvenile hormone in the blood
is reduced through a decrease in its production and by juvenile
hormone-degrading enzymes. With less juvenile hormone present, the insect can
then proceed naturally toward adulthood.In adult insects, juvenile hormone
plays various roles in directing reproductive maturation, such as sperm
production in adult males and egg production in adult females. In social
insects such as termites, juvenile hormone plays an important role in caste
differentiation; for example, high juvenile hormone levels in worker termites cause
them to develop into soldiers. Although the exact mechanism is unclear,
experimental evidence suggests that JHAs may bind to juvenile hormone-degrading
enzymes, the juvenile hormone receptor itself or a combination of both factors.
Whatever the mechanism, JHAs maintain unnaturally high levels of juvenile
hormone within the insect body at a time when it should not naturally be
present. This abnormality has dire consequences on insect survival and
reproduction, severely disrupting the insect's development and/or altering its
reproductive physiology.eg The developmental physiology of immature mosquitoes
and fleas exposed to methoprene is severely altered, resulting in death or
severe developmental abnormalities that eventually lead to death 
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