Studies on Nicotinoids as an Insecticide

Part VII. Cholinesterase Inhibition by Nicotinoids and Pyridylalkyl-amines-Its Significance to Mode of Action

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The inhibition of house fly head cholinesterase by twelve nicotinoids and twenty six pyridylalkylamines was investigated in relation to their ionizations and toxicities to house flies, Musca domestica L. The significant correlation between toxicity and inhibition, and the competitive nature of inhibition indicate that there are some similarities between the receptor for toxic action and the active center of cholinesterase for combining the molecule. Cholinesterase inhibition is shown to be caused by the anionic site binding on the enzyme of the cationic head of the molecule. Hence, the toxic action of nicotine and 3-pyridyl-methylamines is best explained by postulating the nerve receptor carrying the anionic site, which is partly similar to the anionic site of the active center in cholinesterase. The effect on fly nerve activity can also be correlated with the chemical structure. It is shown that the highly toxic nicotinoids should be provided with high but not too high basicity. Dihydronicotyrine having pKa' near the pH of insect body fluid shows the highest toxicity. This can be understood in terms of the preference of free base for penetration and the requirement of ionization for the interaction with the receptor.