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Related Concept Videos

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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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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Direct-Acting Cholinergic Agonists: Pharmacological Actions00:59

Direct-Acting Cholinergic Agonists: Pharmacological Actions

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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...
2.3K
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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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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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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Related Experiment Video

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Subcutaneous Administration of Muscarinic Antagonists and Triple-Immunostaining of the Levator Auris Longus Muscle in Mice
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Choline cannot be replaced by propanolamine in mice.

Zhaoyu Li1, Dennis E Vance

  • 1Department of Biochemistry and Canadian Institutes of Health Research Group on the Molecular and Cell Biology of Lipids, 328 Heritage Medical Research Centre, University of Alberta, Edmonton, Alberta, Canada.

Biochimica Et Biophysica Acta
|February 13, 2007
PubMed
Summary

Propanolamine derivatives cannot replace choline in mice. Studies using choline-deficient mice showed these compounds did not prevent liver damage or restore phosphatidylcholine levels.

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Area of Science:

  • Biochemistry
  • Nutritional Science
  • Animal Models

Background:

  • Choline is an essential nutrient for mammals, obtained through diet or endogenous synthesis via phosphatidylethanolamine N-methyltransferase (PEMT).
  • Pemt(-/-) mice on a choline-deficient diet serve as a model for studying choline's role and potential substitutes in mammals.

Purpose of the Study:

  • To investigate if propanolamine derivatives can substitute for choline in mice, building on findings in yeast.
  • To evaluate the efficacy of 2-amino-propanol, 2-amino-isopropanol, and 3-amino-propanol as choline replacements in a mammalian system.

Main Methods:

  • Utilized Pemt(-/-) mice fed a choline-deficient diet supplemented with various propanolamine derivatives.
  • Analyzed for the formation of phosphatidylpropanolamines and assessed liver health indicators, including liver damage, phosphatidylcholine levels, and fatty liver.

Main Results:

  • No detectable formation of phosphatidylpropanolamines was observed in mice supplemented with propanolamine derivatives.
  • None of the tested propanolamine derivatives prevented liver damage, reduced hepatic phosphatidylcholine levels, or alleviated fatty liver in choline-deficient Pemt(-/-) mice.

Conclusions:

  • Propanolamine derivatives are ineffective as replacements for choline in mice.
  • The study highlights species-specific differences in nutrient requirements and metabolic pathways, particularly concerning choline metabolism.