Mechanisms Of Action Of Insecticides

The great majority of insecticides used today are nerve poisons. This is because insects have highly developed nervous systems and, furthermore, many of their sensory receptors are exposed to the atmosphere outside the insect body. The insect nervous system relies on several key functions that have been exploited as the targets of insecticides: the sodium channel, acetylcholinesterase, the y-aminobutyric acid (GABA) receptor, and the acetylcholine receptor.

The sodium channel, which is the insecticidal target of DDT, pyrethroids, pyrethrins, and other minor classes of insecticides, lines the outer surface of the neurons and functions as the voltage-dependent sodium ion pore (i.e., the pore opens or closes depending on the change in voltage). Upon the arrival of stimuli, this pore allows the selective entry of sodium ions into the neuron for a brief moment and then abruptly shuts down the flow (this phenomenon is called "inactivation"). Thereafter, the sodium channel goes through an internal rearrangement to recover its original state. Such an action causes a brief local equalization of sodium ions between the outside and the inside of the neuron (depolarization), and this change is sensed as a local signal for excitation by the affected neuron. These insecticides delay the shutdown process and furthermore delay the recovery process, resulting in a prolongation of the period of excitation. Insects thus affected continue in a state of hyperexcitation, leading to exhaustion and, at high doses of the insecticide, death.

The next important insecticidal target is acetyl-cholinesterase, which is attacked by organophosphorus and carbamate insecticides. This enzyme, by inducing hydrolysis, inactivates the interneuron nerve transmitter acetylcholine.

This excitatory transmitter is released upon the arrival of a signal from the distal end of one neuron, travels across the intercellular gap, arrives at the frontal end of the second neuron, and reacts with its specific acetylcholine receptor on the surface that sends the signal of excitation to the second neuron. It is important to stress here that such a successful signal transmission must be followed with an abrupt termination of the action of the transmitter; this allows for the second neuron to recover quickly enough and thereby stay ready for the next message, maintaining the normal function of the message-transmitting neuron. This termination action is mainly carried out by acetylcholinesterase, which eliminates acetylcholine from the vicinity of the acetylcholine receptor of the second neuron. All organophosphorus and carbamate insecticides, or their active metabolites, show potent inhibitory actions on acetylcholinesterase of insects as well as other animals. The insects affected by these chemicals show overt signs of excitation, exhaustion and, at sufficient doses, death.

The acetylcholine receptor also can be deactivated to cause the same type of hyperexcitation. Indeed, nicotinoids (which include naturally occurring nicotine analogues and their modern derivatives, sometimes called "neonicotinoids"), such as imidacloprid, are known to directly activate the acetylcholine receptor, just like acetylcholine. Nicotine's excitatory action is well known. Neonicotinoid derivatives readily penetrate the insect's body and nerve sheath, arriving at critical sites of neurons, and persisting there long enough to exert a powerful excitant effect.

The GABA receptor, in contrast, acts as the receiver for the inhibitory transmitter, GABA. That is, unlike acetylcholine, it is not an excitatory transmitter. The signal generated by this GABA-GABA receptor interaction is converted to the opening of chloride channels, which upon the arrival of the signal permit Cl- ions to come into the signal receiving cells (either neurons or muscle cells), to make them nonresponsive to excitation stimuli. Those insecticides—chlorinated hydrocarbon insecticides, cyclodienes (such as y-HCH, dieldrin, endosulfan, toxaphene), and more modern insecticides (such as fipronil)—render the chloride channel inoperative so that chloride ions cannot come into the cells. Cells thus affected fail to receive the inhibitory signal of GABA and therefore cannot counterbalance any excitatory forces. One group of insecticides, avermectin analogues, keep the chloride channel stuck in the open position, an action opposite from that of the excitation-inducing insecticides. These compounds induce long-lasting inhibition of excitation in insects. Insects thus affected by avermectin analogues show diminished activities, nonresponse to stimuli, and slow death through paralysis.

Certainly there are other mechanisms by which normal functions of insects may be affected. The main ones are as follows:

1. Mitochondrial poisons, such as rotenone, which causes respiratory failure.

2. Inhibitors of cuticle formation, via the action of dimilin, including the rest of the diflubenzyron derivatives, which cause difficulty with molting and maintaining protective shields.

3. Insect hormone mimics such as juvenile hormone analogues that keep affected insects as immature forms (this method is effective against insects that cause damage only as adults, e.g., mosquitoes). Another group is ecdysone analogues, which affect insect development, including molting.

4. B. thuringiensis toxins, which mainly affect the potassium channel in insect digestive systems.

5. Formamidine analogues, such as chlordimeform, which mimics octopamine, a naturally occurring transmitter/ hormone, by acting on its receptor. Octopamine is used by insects and mites to control their behavior (among many of its actions), and therefore chlordimeform analogues are known to modify many behavioral patterns of insects and mites, and thereby protect crops from those pests.

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