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Cholinergic Antagonists: Chemistry and Structure-Activity Relationship01:29

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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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Incretins include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which stimulate insulin secretion post-meals. In type 2 diabetes, GIP's efficacy is reduced, making GLP-1 a viable drug target. GIP originates from preproGIP.
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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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Discovering allatostatin type-C receptor specific agonists.

Kübra Kahveci1, Mustafa Barbaros Düzgün1, Abdullah Emre Atis2

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Scientists developed a new pesticide targeting the Allatostatin Type-C Receptor (AlstR-C) for selective control of the pine processionary moth. This breakthrough offers a specific solution for managing this invasive pest, crucial for forestry and public health.

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Area of Science:

  • Entomology
  • Pesticide Development
  • Computational Biology

Background:

  • Pine processionary moth outbreaks are increasing due to climate change, impacting forests and public health.
  • Current control methods for Thaumetopoea pityocampa are non-specific or mechanical.
  • There is a need for targeted insecticides to manage this pest effectively.

Purpose of the Study:

  • To identify a T. pityocampa-specific pesticide targeting the Allatostatin Type-C Receptor (AlstR-C).
  • To develop a novel insecticide with minimal off-target effects.
  • To advance next-generation pesticide design using insect GPCR targets.

Main Methods:

  • Utilized computational biology for target identification.
  • Employed cell-based screening assays to find AlstR-C ligands.
  • Conducted in vivo toxicity and side effect assays for specificity and safety.

Main Results:

  • Identified a series of AlstR-C ligands as potential T. pityocampa-specific insecticides.
  • Demonstrated specificity of the novel agonists to lepidopteran larvae.
  • Confirmed no harmful effects on coleopteran larvae or adults.

Conclusions:

  • This study presents the first AlstR-C targeted pesticide for T. pityocampa.
  • The developed agonists offer a selective and potentially safer alternative to current pest control methods.
  • The approach is applicable to other invertebrate GPCR-targeted pesticide development.