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Related Concept Videos

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

Indirect-Acting Cholinergic Agonists: Chemistry and Structure-Activity Relationship

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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.
Reversible inhibitors display short to medium durations of action. Short-acting agents include simple alcohols with...
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Direct-Acting Cholinergic Agonists: Chemistry and Structure-Activity Relationship01:22

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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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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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Cholinergic Antagonists: Chemistry and Structure-Activity Relationship01:29

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Cholinergic antagonists bind to cholinergic receptors and limit the effects of acetylcholine and other cholinergic agonists. Based on the specific cholinergic receptor affinity, these antagonists are classified as muscarinic or nicotinic. Anticholinergics interrupt parasympathetic innervations while sympathetic innervations remain uninterrupted. Muscarinic antagonists are also called 'muscarinic antagonists', 'antimuscarinics', or 'parasympatholytics'. Nicotinic...
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Related Experiment Video

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Preparation and In Vivo Use of an Activity-based Probe for N-acylethanolamine Acid Amidase
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Acetylcholine Structure-Based Small Activatable Fluorogenic Probe for Specific Detection of Acetylcholinesterase.

Jagpreet S Sidhu1, Kalpana Rajendran1, Abraham B Mathew2

  • 1Department of Inorganic and Physical Chemistry, Indian Institute of Science, Bangalore, Karnataka 560012, India.

Analytical Chemistry
|May 3, 2023
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Summary

Researchers developed a novel naphthalimide-based probe (Naph-3) for early Alzheimer's disease detection. This probe specifically detects acetylcholinesterase (AChE), crucial for AD pathogenesis, and shows potential for inhibitor screening.

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Area of Science:

  • Biochemistry
  • Neuroscience
  • Chemical Biology

Background:

  • Early detection of Alzheimer's disease (AD) is critical for managing its progression.
  • Acetylcholinesterase (AChE) is a key enzyme implicated in AD pathogenesis.
  • Distinguishing AChE from butyrylcholinesterase (BuChE) is essential for accurate diagnostics.

Purpose of the Study:

  • To design and synthesize novel naphthalimide-based fluorogenic probes for specific AChE detection.
  • To evaluate the probe's specificity against BuChE.
  • To assess the probe's utility in cell-based assays and inhibitor screening.

Main Methods:

  • Utilized an "acetylcholine-mimic" approach for probe design.
  • Synthesized a new class of naphthalimide (Naph)-based fluorogenic probes.
  • Investigated probe activity using Electrophorus electricus AChE and purified human brain AChE.
  • Performed cell membrane permeability and fluorescence assays in Neuro-2a cells.

Main Results:

  • The probe Naph-3 demonstrated significant fluorescence enhancement upon reaction with AChE.
  • Naph-3 showed high specificity, largely avoiding interference from BuChE.
  • Naph-3 successfully penetrated Neuro-2a cell membranes and detected endogenous AChE.
  • The probe proved effective for screening AChE inhibitors.

Conclusions:

  • Developed a novel naphthalimide-based fluorogenic probe (Naph-3) for specific AChE detection.
  • Naph-3 offers a promising tool for early AD diagnosis and related complication assessment.
  • The study opens new avenues for developing diagnostic and therapeutic strategies targeting AChE.