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Indirect-Acting Cholinergic Agonists: Mechanism of Action01:18

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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 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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Cholinergic Receptors: Nicotinic01:15

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Nicotinic receptors are ligand-gated ion channels that are activated by acetylcholine and nicotine. Upon activation, they cause a rapid increase in the permeability of cells to K+, Na+, and Ca2+, followed by depolarization and excitation. They are in the autonomic ganglia, skeletal neuromuscular junction, CNS, and adrenal medulla.
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Cholinergic Receptors: Muscarinic01:25

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The pharmacological actions of acetylcholine are elicited via its binding to two families of cholinergic receptors or cholinoceptors, namely, muscarinic and nicotinic receptors. Muscarinic receptors are G protein-coupled receptors and have five subtypes, M1–M5. All mAChR subtypes are activated by acetylcholine and blocked by the antagonist, atropine. 
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Direct-acting cholinergic agonists, such as synthetic choline esters and naturally occurring alkaloids, exert their effects by enhancing the actions of acetylcholine and stimulating the parasympathetic nervous system. Synthetic choline esters share structural similarities with acetylcholine. For example, they have a positively charged quaternary ammonium or onium group, contributing to their hydrophilic characteristics. As a result, they are poorly absorbed in the body through oral...
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Direct-Acting Cholinergic Agonists: Pharmacological Actions00:59

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Direct-acting cholinergic agonists exert their pharmacological actions by mimicking the effects of acetylcholine on postsynaptic muscarinic receptors to generate parasympathetic responses. These agents elicit a range of physiological responses, including cardiovascular effects. For example, activation of muscarinic receptors induces bradycardia, decreased cardiac output, reduced peripheral resistance, and consequent hypotension. In the eye, stimulation of M3 receptors leads to smooth muscle...
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Real-time activation of central cholinergic circuits during recognition memory.

Sonia Bonnì1, Viviana Ponzo1, Francesco Di Lorenzo1

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The European Journal of Neuroscience
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Summary

Short latency afferent inhibition (SAI), a marker of brain acetylcholine activity, increases during memory retrieval. This finding suggests SAI modulation by memory tasks, offering a new neurophysiological marker for cognitive processes.

Keywords:
acetylcholinememoryretrievalshort latency afferent inhibition

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Area of Science:

  • Neuroscience
  • Cognitive Science
  • Neurophysiology

Background:

  • Short latency afferent inhibition (SAI) is a transcranial magnetic stimulation (TMS) protocol reflecting central cholinergic activity.
  • Acetylcholine plays a key role in memory processes.
  • The impact of memory tasks on SAI has not been previously studied.

Purpose of the Study:

  • To investigate the modulation of SAI circuits during a recognition memory task (RMT).
  • To determine if SAI can serve as a neurophysiological marker for memory-related cholinergic activity.

Main Methods:

  • Healthy subjects performed a computerized non-verbal RMT involving face recognition.
  • SAI was measured during baseline, encoding, consolidation, retrieval, and post-task phases.
  • A control task involving visual feature judgment was used for comparison.

Main Results:

  • SAI significantly increased during the retrieval phase of the RMT compared to baseline.
  • No significant changes in SAI were observed during the control task.
  • These results indicate that SAI is modulated by active memory processes.

Conclusions:

  • Ongoing memory processes can modulate SAI.
  • SAI shows potential as a neurophysiological marker of central cholinergic activity during memory tasks.