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Related Concept Videos

Indirect-Acting Cholinergic Agonists: Pharmacological Actions01:30

Indirect-Acting Cholinergic Agonists: Pharmacological Actions

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Indirect-acting cholinergic agonists, also known as anticholinesterases, exert their pharmacological effects by enhancing cholinergic transmission in various body parts, including the neuromuscular junction, autonomic cholinergic synapses, and the brain.
At the neuromuscular junction, these agents work by inhibiting the breakdown of acetylcholine, allowing it to remain bound to the receptor and bind to nearby receptors. This process leads to repetitive firing of the endplate, causing muscle...
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Direct-Acting Cholinergic Agonists: Therapeutic Uses01:11

Direct-Acting Cholinergic Agonists: Therapeutic Uses

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Direct-acting cholinergic agonists have many therapeutic uses in various medical fields. Choline esters, including acetylcholine, have limited clinical utility due to their non-selectivity and short duration of action. Still, acetylcholine and carbachol are applied topically during ophthalmologic surgery to induce miosis. Pilocarpine, a muscarinic and ganglionic stimulator, effectively treats open-angle glaucoma and alleviates xerostomia and dry mouth caused by radiotherapy or Sjögren...
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Parkinson's Disease: Treatment01:24

Parkinson's Disease: Treatment

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Neurodegenerative disorders, such as Parkinson's Disease (PD), involve the gradual and irreversible destruction of neurons in particular brain areas. These disorders exhibit standard features like proteinopathies, selective vulnerability of some neurons, and an interaction of intrinsic properties, genetics, and environmental influences in neural injury.
Parkinson's Disease is primarily a result of the loss of dopaminergic neurons in the substantia nigra pars compacta. The cornerstone of...
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Direct-Acting Cholinergic Agonists: Pharmacokinetics01:31

Direct-Acting Cholinergic Agonists: Pharmacokinetics

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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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Anticholinesterase Agents: Poisoning and Treatment01:26

Anticholinesterase Agents: Poisoning and Treatment

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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.     
Irreversible agents form a strong bond with the cholinesterase enzyme, making it inactive. The breakdown of the phosphorylated enzyme is...
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Direct-Acting Cholinergic Agonists: Chemistry and Structure-Activity Relationship01:22

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

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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.
The direct-acting...
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Related Experiment Video

Updated: Jun 28, 2025

Comprehensive Profiling of Dopamine Regulation in Substantia Nigra and Ventral Tegmental Area
09:54

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Published on: August 10, 2012

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Ivermectin increases striatal cholinergic activity to facilitate dopamine terminal function.

Hillary A Wadsworth1, Alicia M P Warnecke2, Joshua C Barlow1

  • 1Department of Cellular Biology and Physiology, and Neuroscience Program, Brigham Young University, 4005 LSB, Provo, UT, 84602, USA.

Cell & Bioscience
|April 17, 2024
PubMed
Summary

Ivermectin (IVM) enhances dopamine release in the brain by increasing the excitability of dopamine terminals, primarily through enhanced cholinergic activity. This finding suggests a novel mechanism for IVM

Keywords:
FSCVIvermectinParkinson’sPurinergic P2X4 receptorsReceptors

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A Computerized Test Battery to Study Pharmacodynamic Effects on the Central Nervous System of Cholinergic Drugs in Early Phase Drug Development
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Presynaptic Dopamine Dynamics in Striatal Brain Slices with Fast-scan Cyclic Voltammetry
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Related Experiment Videos

Last Updated: Jun 28, 2025

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A Computerized Test Battery to Study Pharmacodynamic Effects on the Central Nervous System of Cholinergic Drugs in Early Phase Drug Development
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Presynaptic Dopamine Dynamics in Striatal Brain Slices with Fast-scan Cyclic Voltammetry
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Presynaptic Dopamine Dynamics in Striatal Brain Slices with Fast-scan Cyclic Voltammetry

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Area of Science:

  • Neuroscience
  • Pharmacology

Background:

  • Ivermectin (IVM) is an antiparasitic drug known to affect invertebrate ion channels.
  • IVM also modulates vertebrate ion channels and shows preclinical promise for Parkinson's disease treatment, potentially by enhancing L-DOPA therapy.
  • The precise mechanisms by which IVM influences dopamine terminal function are not fully understood.

Purpose of the Study:

  • To investigate the pharmacological effects of Ivermectin on dopamine terminal function.
  • To determine the role of purinergic P2X4 and nicotinic acetylcholine receptors in mediating IVM's effects on dopamine release.
  • To elucidate how IVM influences dopamine release in the context of L-DOPA treatment.

Main Methods:

  • Electrochemical detection was used to measure dopamine release in the dorsal striatum.
  • Experiments involved inactivating P2X4 receptors and antagonizing nicotinic receptors to assess their role in IVM's effects.
  • Cholinergic interneuron firing was monitored to evaluate IVM's impact on neuronal activity.
  • Co-application of L-DOPA and IVM was performed to assess combined effects on dopamine release.

Main Results:

  • Ivermectin significantly enhanced dopamine release in the dorsal striatum.
  • IVM's effects on dopamine release were not dependent on P2X4 receptors but were blocked by nicotinic receptor antagonism.
  • IVM enhanced striatal cholinergic interneuron firing.
  • Combined L-DOPA and IVM treatment increased dopamine release, with a shift suggesting enhanced terminal excitability rather than increased vesicular content.

Conclusions:

  • Ivermectin increases striatal dopamine release primarily by enhancing cholinergic activity that affects dopamine terminals.
  • The mechanism involves increased terminal excitability rather than alterations in vesicular dopamine content.
  • These findings highlight a novel role for IVM in modulating dopaminergic neurotransmission, with implications for Parkinson's disease research.