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Indirect-Acting Cholinergic Agonists: Chemistry and Structure-Activity Relationship01:29

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Indirect-acting cholinergic agonists are agents that interact with the acetylcholinesterase enzyme in the synaptic cleft, preventing the breakdown of acetylcholine into choline and acetate. Consequently, the concentration of acetylcholine in the synaptic cleft increases. These agonists can be classified into reversible and irreversible inhibitors based on their duration of action.
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Indirect-acting cholinergic agonists work by interacting with an enzyme called acetylcholinesterase (AChE) in the synaptic cleft. They can be reversible or irreversible inhibitors and have different effects on the enzyme.
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Anticholinesterases, also known as cholinesterase inhibitors, work by blocking the breakdown of acetylcholine, leading to its accumulation in the synaptic cleft. This accumulation indirectly enhances both muscarinic and nicotinic actions. These agents are classified as reversible or irreversible based on their mechanism of action.     
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Cholinergic agonists or cholinomimetics mimic the action of acetylcholine to stimulate the parasympathetic nervous system. They are categorized into direct-acting and indirect-acting agents. The direct-acting cholinergic drugs induce the parasympathetic response by directly binding to the muscarinic or nicotine receptors. In comparison, the indirect-acting cholinergic drugs prevent acetylcholine hydrolysis, indirectly contributing to the extended parasympathetic response.
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Avocado Sample Preparation Using the QuEChERS Method with Ammonium Formate for Pesticide Analysis
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Statement on the active substance acetamiprid.

, Antonio Hernandez Jerez, Paulien Adriaanse

    EFSA Journal. European Food Safety Authority
    |February 2, 2022
    PubMed
    Summary
    This summary is machine-generated.

    The European Food Safety Authority (EFSA) reviewed studies on the pesticide acetamiprid, finding no conclusive evidence of higher human or environmental risks. However, further assessment of endocrine-disrupting properties and risks to birds and bees is recommended.

    Keywords:
    acetamipridaquatic organismsbeesbirdsendocrine disruptionenvironmental risk assessmentexpert knowledge elicitationinsecticidesneonicotinoidssoil organismsuncertainty analysis

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    Area of Science:

    • Environmental Science
    • Toxicology
    • Risk Assessment

    Background:

    • Acetamiprid, an insecticidal pesticide, is undergoing regulatory review (AIR3).
    • Concerns regarding potential human and environmental risks prompted a request to restrict its uses.
    • The European Food Safety Authority (EFSA) Panel on Plant Protection Products and their Residues (PPR Panel) was mandated to evaluate new evidence.

    Purpose of the Study:

    • To assess new evidence on acetamiprid hazards and exposure compared to previous EU evaluations.
    • To advise on whether existing literature proves serious risks to humans or the environment.
    • To guide regulatory decisions on acetamiprid's continued use.

    Main Methods:

    • A stepwise methodology was employed, including literature screening, data extraction, and critical appraisal.
    • Weight of evidence analysis considered previous EU assessments.
    • Uncertainty analysis and expert knowledge elicitation were utilized.

    Main Results:

    • No conclusive evidence of higher human health hazards (genotoxicity, developmental, neurotoxicity, immunotoxicity) was found.
    • The PPR Panel recommends assessing acetamiprid's endocrine-disrupting properties.
    • No conclusive evidence of higher environmental hazards for birds, aquatic organisms, bees, or soil organisms was found.

    Conclusions:

    • Current evidence does not confirm higher human health risks from acetamiprid.
    • Further investigation into endocrine disruption potential is warranted.
    • Potential risks to birds and bees require additional consideration despite lack of conclusive evidence.