17. IRAC Group/Mode of Action

What is a chemical family?

A group of pesticides with similar chemical structures and related properties.

What is an IRAC group?

IRAC group, groups insecticides by their target site/mode of action,

developed to help manage insecticide resistance.

What is an active constituent?

The chemical in a pesticide product that produces the pest-control effect.

Example: Bifenthrin

What is a mode of action (MoA)?

The specific way an active constituent affects a pest’s biological system.

Easy memory:
MoA = how it works

What is a target site?

The specific protein, receptor, channel, enzyme or biological process that the pesticide acts on.

Easy memory:
Target = what it acts on

How do chemical family, active constituent, IRAC group and MoA fit together?

Synthetic pyrethroid = chemical family
↓
IRAC 3A = IRAC group
↓
Voltage-gated sodium channel = target
↓
Keeps sodium channels open longer = mode of action
↓
Bifenthrin = active constituent

Label the diagram of the Basic Nerve Structure

What is a neuron?

A nerve cell that receives and transmits signals.

What is a presynaptic neuron?

The neuron that sends the signal and releases neurotransmitter.

What is a postsynaptic neuron?

The neuron that receives the neurotransmitter signal.

What is a synapse?

The junction where one neuron communicates with another cell.

What is the synaptic cleft?

The tiny gap between the presynaptic and postsynaptic cells.

What is a synaptic vesicle?

A tiny sac inside the presynaptic nerve ending that stores neurotransmitter.

What is a neurotransmitter?

A chemical messenger released by a neuron that carries a signal across the synaptic cleft.

What are examples of important Neurotransmitters for Pest control;

Acetylcholine

Gaba

Glutamate

What is excitation?

What’s another name for it

An effect that makes a neuron more likely to fire.

depolarisation

What is inhibition?

What’s another name for it

An effect that makes a neuron less likely to fire.

hyperpolarisation

What is depolarisation?

The inside of the nerve becomes less negative/more positive, making nerve firing more likely.

What is hyperpolarisation?

The inside of the nerve becomes more negative, making nerve firing less likely.

Hyperpolarise = inhibit

What is a receptor?

A protein that recognises and responds to a specific chemical signal.

What is an ion channel?

A protein that forms a gate allowing specific ions to cross a cell membrane.

What is a voltage-gated sodium channel?

A channel found on the axons of nerves that opens in response to electrical changes and allows Na⁺ into the nerve, helping the nerve impulse travel.

What two IRAC groups act on the Voltage gated sodium channels

3A and 22A

What is a voltage-gated calcium channel?

A channel that opens at the nerve ending and allows Ca²⁺ into the neuron, triggering neurotransmitter release.

What is a nicotinic acetylcholine receptor (nAChR)?

A receptor/channel activated by acetylcholine, allowing positive ions (Na ions) into the cell and causing nerve stimulation.

What two IRAC groups act on the Nicotinic acetylcholine receptor (nAChR)?

4A and 5

What is a GABA-gated chloride channel?

A channel opened by GABA, allowing chloride ions to inhibit nerve activity.

What two IRAC groups act on the GABA-gated chloride channel

2B and 30

What is a glutamate-gated chloride channel (GluCl)?

An insect nerve channel activated by glutamate that allows Cl⁻ into the nerve and inhibits nerve activity.

What IRAC groups act on the GABA-gated chloride channel

IRAC 6

What is acetylcholine (ACh)?

A neurotransmitter used to send signals between nerve cells.

What is acetylcholinesterase (AChE)?

An enzyme that breaks down acetylcholine after it has transmitted its signal.

What happens if AChE (acetylcholinesterase) is inhibited?

Acetylcholine builds up in the synapse → receptors keep being stimulated → continuous nerve activity → paralysis/death.

What IRAC groups act on the acetylcholinesterase

1A and 1B

What is an agonist?

A chemical that activates a receptor.

What is an antagonist?

A chemical that blocks a receptor from being activated.

What is an inhibitor?

Something that reduces or stops the activity of an enzyme or biological process.

Example IRAC group 1a and 1b stops Acetylcholinesterase from breaking down acetylcholine

What is a modulator?

A chemical that changes how a receptor or channel functions.

It may increase, decrease or alter its normal activity.

What is the difference between a neurotransmitter and a ligand?

Neurotransmitter = chemical messenger released by a neuron.
Ligand = any chemical that binds to a receptor.

Acetylcholine (ACh) = neurotransmitter + ligand for acetylcholine receptors
GABA = neurotransmitter + ligand for GABA receptors
Glutamate = neurotransmitter + ligand for glutamate receptors

What is a Ryanodine receptor (RyR)?

A calcium-release channel inside muscle cells that releases stored Ca²⁺ to control muscle contraction.

What happens when RyR is abnormally activated?

What IRAc group is responsible for this

Too much Ca²⁺ is released → calcium stores become depleted → muscles cannot function normally → Flaccid paralysis/death.

IRAC group 28

What is a mitochondria

What is ATP

produces energy for the cell

Molecule that is used for energy

What is the electron transport chain?

A series of proteins in the inner mitochondrial membrane that transfer electrons and use their energy to pump H⁺ ions and build a proton gradient.

hat is a proton gradient?

A buildup of H⁺ ions on one side of the inner mitochondrial membrane, storing potential energy.

What is ATP synthase?

An enzyme that allows H⁺ to flow back across the mitochondrial membrane and uses that energy to make ATP.

What is juvenile hormone?

An insect hormone that helps maintain immature characteristics during development.

What happens if juvenile hormone signalling is disrupted? Stay elevated

Normal development and metamorphosis are disrupted (stays elevated), so the insect may fail to develop into a normal adult.

What IRAC group is responsible for Juvenile hormone disruption

IRAC 7A/B/C

What is chitin synthase (CHS1)?

What IRAC group does this relate to?

An enzyme involved in making chitin for the new insect cuticle during moulting.

IRAC 15

What happens if chitin synthesis is inhibited?

The insect cannot form its new exoskeleton properly → moulting fails → death/development failure.

Name the Main IRAC group and chemical family in pest control

1a Carbamates

1b Organophosphates

2a Phenylpyrazoles

3a Synthetic Pyrethroid

4a Neonicotinoids

5 Spinosyns

6 Avermectins / Milbemycins
7 a,b,c Juvenile Hormone Modulators

13 Pyrroles

15 Benzoylureas

20a Hydramethylnon

22A Oxadiazines

28 Diamides

30 Meta-diamides/Isoxazolines

Chemical Family for 1a

Carbamates

Chemical Family for 1b

Organophosphates

Chemical Family for 2a

Phenylpyrazoles

Chemical Family for 3a

Synthetic Pyrethroid

Chemical Family for 4a

Neonicotinoids

Chemical Family for 5

Spinosyns

Chemical Family for 6

Avermectins / Milbemycins

Chemical Family for 7a, 7b and 7 c

Juvenile Hormone Modulators

Chemical Family for 13

Pyrroles

Chemical Family for 15

Benzoylureas

Chemical Family for 20a

Hydramethylnon

Chemical Family for 22a

Oxadiazines

Chemical Family for 28

Diamides

Chemical Family for 30

Meta-diamides/Isoxazolines

IRAC group for Diamides

28

IRAC group for Meta-diamides/Isoxazolines

30

IRAC group for Hydramethylnon

20a

IRAC group for Spinosyns

5

IRAC group for Oxadiazines

22a

IRAC group for Benzoylureas

15

IRAC group for Synthetic Pyrethroid

3a

IRAC group for Carbomate’s

1a

IRAC group for Phenylpyrazoles

2a

IRAC group for Organophosphates

1b

IRAC group for Juvenile Hormone Modulators

7a, 7b and 7c

IRAC group for Neonicotinoids

4a

IRAC group for Avermectins / Milbemycins

6

IRAC group for Pyrroles

13

Main active constituent for

IRAC	Chemical family	Active to memorise
1A	Carbamates
1B	Organophosphates
2B	Phenylpyrazoles / Fiproles
3A	Synthetic pyrethroids
4A	Neonicotinoids
5	Spinosyns
6	Avermectins / Milbemycins
7A	Juvenile hormone analogues
7B	Fenoxycarb
7C	Pyriproxyfen
13	Pyrroles
15	Benzoylureas
20A	Hydramethylnon
22A	Oxadiazines
28	Diamides
30	Meta-diamides / Isoxazolines

IRAC	Chemical family	Active to memorise
1A	Carbamates	Bendiocarb
1B	Organophosphates	Chlorpyrifos*
2B	Phenylpyrazoles / Fiproles	Fipronil
3A	Synthetic pyrethroids	Bifenthrin
4A	Neonicotinoids	Dinotefuran
5	Spinosyns	Spinosad
6	Avermectins / Milbemycins	Abamectin
7A	Juvenile hormone analogues	Methoprene
7B	Fenoxycarb	Fenoxycarb
7C	Pyriproxyfen	Pyriproxyfen
13	Pyrroles	Chlorfenapyr
15	Benzoylureas	Chlorfluazuron
20A	Hydramethylnon	Hydramethylnon
22A	Oxadiazines	Indoxacarb
28	Diamides	Chlorantraniliprole
30	Meta-diamides / Isoxazolines	Broflanilide

IRAC 1A — What is the main target and simple mode of action?

Target: Acetylcholinesterase (AChE)
MoA: Inhibits AChE → acetylcholine builds up → nerves stay stimulated → paralysis/death

IRAC 1B — What is the main target and simple mode of action?

Target: Acetylcholinesterase (AChE)
MoA: Inhibits AChE → acetylcholine builds up → nerves stay stimulated → paralysis/death

IRAC 2B — What is the main target and simple mode of action?

Target: GABA-gated chloride channels
MoA: Blocks GABA chloride channels → nerve inhibition fails → overexcitation → paralysis/death

IRAC 3A — What is the main target and simple mode of action?

Target: Voltage-gated sodium channels
MoA: Keeps sodium channels open longer → repeated nerve firing → paralysis/death

IRAC 4A — What is the main target and simple mode of action?

Target: Nicotinic acetylcholine receptors
MoA: Overstimulates nicotinic receptors → nerves keep firing → paralysis/death

IRAC 5 — What is the main target and simple mode of action?

Target: Nicotinic acetylcholine receptors
MoA: Overstimulates nicotinic receptors → nerves keep firing → paralysis/death

IRAC 6 — What is the main target and simple mode of action?

Target: Glutamate-gated chloride channels
MoA: Opens chloride channels → nerve activity is suppressed → flaccid paralysis/death

IRAC 7A/B/C — What is the main target and simple mode of action?

Target: Juvenile hormone receptors
MoA: Mimics juvenile hormone → normal development and metamorphosis are disrupted

IRAC 13 — What is the main target and simple mode of action?

Target: Mitochondria
MoA: Disrupts the proton gradient → ATP production fails → energy failure/death

IRAC 15 — What is the main target and simple mode of action?

Target: Chitin synthesis
MoA: Blocks chitin production → new exoskeleton cannot form properly → moulting fails

IRAC 20A — What is the main target and simple mode of action?

Target: Mitochondrial electron transport
MoA: Blocks electron transport → ATP production falls → energy failure/death

IRAC 22A — What is the main target and simple mode of action?

Target: Voltage-gated sodium channels
MoA: Blocks sodium channels → nerves cannot fire properly → paralysis/death

IRAC 28 — What is the main target and simple mode of action?

Target: Ryanodine receptors in muscle cells
MoA: Causes uncontrolled calcium release → muscles cells eventually depleted of calcium → no muscle contraction → flaccid paralysis/death

IRAC 30 — What is the main target and simple mode of action?

Target: GABA-gated chloride channels
MoA: Blocks GABA chloride channels → nerve inhibition fails → overexcitation → paralysis/death

Which IRAC groups have related targets?

• 1A & 1B → AChE

• 2B & 30 → GABA-gated chloride channels

• 3A & 22A → voltage-gated sodium channels

• 4A & 5 → nicotinic acetylcholine receptors

• 13 & 20A → mitochondrial energy production

IRAC 1A vs 1B — what is similar?

Both inhibit acetylcholinesterase (AChE) → acetylcholine builds up → continuous nerve stimulation.

IRAC 2B vs 30 — what is similar?

Both interfere with GABA-gated chloride channels → nerve inhibition fails → overexcitation/paralysis.
They act at different sites/mechanisms, which is why they are separate IRAC groups.