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Related Concept Videos

Local Anesthetics: Pharmacokinetics01:13

Local Anesthetics: Pharmacokinetics

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The potency and duration of action of local anesthetics (LAs) are determined by their pharmacokinetics. Pharmacokinetics describes how LAs are absorbed, distributed, metabolized, and eliminated from the body. When administered to the vascular tissues, LAs are quickly absorbed and enter the systemic circulation, reducing their localized effects. Adding vasoconstrictors such as epinephrine to LAs reduces their absorption into the systemic circulation, making them clinically effective. The...
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Inhalational Anesthetics: Overview01:20

Inhalational Anesthetics: Overview

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Inhalation anesthetics are drugs that induce general anesthesia upon inhalation. They work by increasing the sensitivity of GABAA receptors or inhibiting NMDA receptors, leading to a decrease in central nervous system activity. The depth of anesthesia can be rapidly adjusted by changing the concentration of the inhaled gas. Some common examples of inhalational anesthetics include volatile liquids like isoflurane, desflurane, sevoflurane and gases like xenon and nitrous oxide. Isoflurane, a...
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Parenteral Anesthetics: Overview01:24

Parenteral Anesthetics: Overview

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Intravenous anesthetics are drugs administered parenterally to induce anesthesia or sedation. Propofol is a widely used agent formulated as a 1% emulsion in soybean oil, glycerol, and egg phosphatide. It induces rapid anesthesia primarily due to its rapid distribution from the bloodstream to target tissues and is metabolized in the liver. However, it can cause significant pain on injection and hypertriglyceridemia. Fospropofol, a water-based prodrug of propofol, lacks these adverse effects.
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Local Anesthetics: Mechanism of Action01:23

Local Anesthetics: Mechanism of Action

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Local anesthetics (LAs) block sensory and motor impulses by inhibiting the sodium channels on the nerve cell membranes. This induces temporary loss of sensation, relieving pain in a specific body area.
Local anesthetics are amphiphilic molecules consisting of a hydrophobic aromatic part linked to a hydrophilic group by an ester or amide linkage. They are weak bases and are usually available as salts, which increases their solubility and stability. Once administered, LAs exist in the body either...
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Local Anesthetics: Adverse Effects01:12

Local Anesthetics: Adverse Effects

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While local anesthetics are generally safe and well-tolerated, they can occasionally cause adverse effects that vary in severity. Local anesthetics can induce toxicity at two distinct levels. They can either produce local effects through direct contact with the neural elements or be absorbed into the bloodstream from the injection site, leading to systemic effects.
Once absorbed into the systemic circulation, local anesthetics can affect the organs that depend on the functioning of sodium...
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Local Anesthetics: Common Agents and Their Applications01:23

Local Anesthetics: Common Agents and Their Applications

989
Local anesthetics (LAs) are commonly used for various applications in medical and dental procedures. Some of the common agents used are cocaine, lidocaine, and bupivacaine.
Cocaine is an ester of benzoic acid and methylecgogine. It is used to anesthetize and vasoconstrict locally. Currently, it is used primarily for topical applications. It is beneficial for surgeries on the upper respiratory tract, providing anesthesia and shrinking the mucosa. Cocaine in the form of cocaine hydrochloride is...
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Electrocardiogram Recordings in Anesthetized Mice using Lead II
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Electrocardiogram Recordings in Anesthetized Mice using Lead II

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Fluorescent Anesthetics.

Daniel J Emerson1, Ivan J Dmochowski1

  • 1University of Pennsylvania, Philadelphia, PA, United States.

Methods in Enzymology
|April 21, 2018
PubMed
Summary
This summary is machine-generated.

New imaging tools, 1-aminoanthracene (1-AMA) and 1-azidoanthracene (1-AZA), visualize general anesthetic distribution in cells and tissues. These compounds also help identify anesthetic protein targets for drug discovery.

Keywords:
1-Aminoanthracene1-AzidoanthraceneCaged anestheticConfocal microscopyFluorescent probe

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Area of Science:

  • Neuroscience
  • Pharmacology
  • Biochemistry

Background:

  • General anesthetics modulate GABAA chloride currents, leading to sedation and immobilization.
  • Understanding anesthetic distribution and target engagement is crucial for developing safer and more effective anesthetic agents.
  • Current methods for visualizing anesthetic distribution and identifying protein targets are limited.

Purpose of the Study:

  • To introduce novel imaging tools, 1-aminoanthracene (1-AMA) and its photoactive derivative 1-azidoanthracene (1-AZA), for studying general anesthetics.
  • To demonstrate the utility of 1-AMA and 1-AZA in visualizing anesthetic distribution in cells and tissues.
  • To showcase the application of 1-AZA in identifying and characterizing anesthetic-protein interactions.

Main Methods:

  • Utilized 1-aminoanthracene (1-AMA) as an exogenous fluorophore and general anesthetic.
  • Employed 1-azidoanthracene (1-AZA) for optogenetic control and target identification via photoaffinity labeling.
  • Applied imaging assays to visualize cellular and tissue distribution of anesthetics.
  • Used binding assays for screening and characterizing anesthetic-protein targets.

Main Results:

  • 1-AMA potentiates GABAA chloride currents and immobilizes Xenopus laevis tadpoles.
  • Cellular and tissue anesthetic distribution was successfully imaged, allowing quantification of on- and off-pathway targets.
  • 1-AZA demonstrated shared targets with 1-AMA and provided spatial and temporal control over anesthetic effects via near-UV laser irradiation.
  • 1-AZA adduction enabled screening of potential protein targets and characterization of binding sites.

Conclusions:

  • 1-AMA and 1-AZA are valuable tools for visualizing general anesthetic distribution and action.
  • These compounds facilitate the identification and characterization of anesthetic targets, aiding in the development of new anesthetic drugs.
  • The presented imaging and binding assays demonstrate the broad utility of 1-AMA and 1-AZA in pharmacological research.