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Related Concept Videos

Agonism and Antagonism: Quantification01:14

Agonism and Antagonism: Quantification

When drugs are administered, they can elicit either an agonist or antagonist effect on the body. Agonism occurs when a drug activates a specific receptor, triggering a biological response. On the other hand, antagonism happens when a drug binds to the same receptors but blocks their activation, thereby preventing a biological response.
To quantify these effects, researchers use a dose-response curve, which provides valuable information about the potency and efficacy of a drug. Potency refers to...
Drug-Receptor Interaction: Agonist01:25

Drug-Receptor Interaction: Agonist

Agonists are drugs that interact with specific receptors in the body to produce a biological response. When an agonist binds to a receptor, it activates or enhances the receptor's function, leading to physiological effects. The interaction between agonist drugs and receptors is crucial for their therapeutic action in various medical treatments.
Agonists can bind to receptors in different ways. Some agonists bind directly to the receptor's active site, mimicking the endogenous ligand's action.
Adrenergic Agonists: Chemistry and Structure-Activity Relationship01:16

Adrenergic Agonists: Chemistry and Structure-Activity Relationship

Adrenergic agonists' structure-activity relationship (SAR) determines their selectivity and efficacy. These agonists comprise a phenylethylamine moiety with an aromatic ring and an ethylamine side chain.
Aromatic ring substitutions: Substituting the aromatic ring with –OH groups at positions 3 and 4 yields catecholamines (e.g., epinephrine), which have a high affinity for adrenoceptors. Hydrogen bonding between –OH groups and receptors enhances adrenergic activity.
Separation of the aromatic...
Drug-Receptor Interactions01:29

Drug-Receptor Interactions

Drug-receptor interaction describes the binding of receptors by drugs, but not all drug-receptor interactions result in activation and tissue response. For instance, the binding of agonists activates the receptor to generate a cellular reaction, while antagonists bind to receptors without causing their activation.
Several parameters, such as the drug's affinity for its receptor and its efficacy, which is its ability to activate the receptor, determine the drug's effect on the tissue.
Drug Concentrations: Measurements01:23

Drug Concentrations: Measurements

Drug concentration is the quantity of a drug present in a biological sample. Measuring drug amounts in biological samples allows the clinician to understand how a drug is absorbed, distributed, metabolized, and excreted. Samples can be obtained through invasive or non-invasive methods. Invasive techniques involve surgical or parenteral interventions to gather blood, cerebrospinal fluid, or tissue biopsy. Conversely, non-invasive approaches provide samples like urine, feces, and saliva.
Plasma —...
Adrenergic Agonists: Mixed-Action Agents01:28

Adrenergic Agonists: Mixed-Action Agents

Mixed-action adrenergic agonists, like ephedrine and pseudoephedrine, directly and indirectly affect adrenergic receptors. These agents stimulate adrenoceptors and indirectly release stored neurotransmitters, amplifying the adrenergic response.
Ephedrine and pseudoephedrine lack a catecholamine group, making them less susceptible to degradation by metabolic enzymes. They have increased oral bioavailability and lipophilicity, resulting in a longer duration of action. Their response is reduced by...

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Stepwise Dosing Protocol for Increased Throughput in Label-Free Impedance-Based GPCR Assays
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Published on: February 21, 2020

Generalized concentration addition: a method for examining mixtures containing partial agonists.

Gregory J Howard1, Thomas F Webster

  • 1Department of Environmental Health, Boston University School of Public Health, 715 Albany Street, Boston, MA 02118, USA. gh@bu.edu

Journal of Theoretical Biology
|April 7, 2009
PubMed
Summary
This summary is machine-generated.

Predicting toxic chemical mixture effects is crucial. Generalized concentration addition extends methods to assess interactions, including partial agonists, for better risk assessment.

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Quantifying Agonist Activity at G Protein-coupled Receptors
11:45

Quantifying Agonist Activity at G Protein-coupled Receptors

Published on: December 26, 2011

Area of Science:

  • Toxicology
  • Environmental Health
  • Pharmacology

Background:

  • Environmental exposures frequently involve multiple toxic agents simultaneously.
  • Accurate prediction of combined toxicant effects is essential for risk assessment and determining synergy or antagonism.
  • Concentration addition (CA) is a standard method for similarly acting chemicals but is limited with partial agonists.

Purpose of the Study:

  • To propose an extension of concentration addition for mixtures containing full and partial agonists.
  • To introduce 'generalized concentration addition' (GCA) for assessing combined toxicant effects.
  • To evaluate GCA's applicability to dose-response relationships described by Hill functions.

Main Methods:

  • Developed a functional form extending concentration addition to accommodate partial agonists.
  • Applied the generalized concentration addition model to agents with Hill dose-response functions (n=1).
  • Utilized mechanistic ligand-receptor models to validate GCA predictions for various agonist/antagonist combinations.

Main Results:

  • The proposed generalized concentration addition model produces linear isoboles (curves of constant joint effect) with positive, negative, or zero slopes.
  • This model successfully predicts joint effects for mixtures including full agonists and partial agonists.
  • Special cases, such as combinations of two full agonists or a full agonist with a competitive antagonist, were accurately represented.

Conclusions:

  • Generalized concentration addition provides a flexible framework for analyzing toxicant mixtures with diverse agonist properties.
  • This extended method allows for accurate prediction of mixture toxicity and the identification of synergistic or antagonistic interactions.
  • GCA is a valuable tool for environmental risk assessment and understanding complex chemical exposures.