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Agonists can bind with and activate receptors, resulting in the formation of drug-receptor complexes. Once formed, these complexes catalyze many biochemical processes at the cellular level and subsequently induce a pharmacologic response. The degree of response is directly proportional to the fraction of activated receptors, which in turn, depends on the concentration of the drug at the receptor site as well as the sensitivity of the receptor. An increase in the administered dose contributes to...
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The potency of a drug is the measure of its ability to produce a biological response and can be compared by looking at the half-maximum effective concentration or EC50 values of different drugs. A lower EC50 value indicates higher potency of the drug. In the dose–response curve of two antihypertensive drugs, candesartan and irbesartan, a significant difference is observed in their EC50 values. A lower EC50 value for candesartan indicates that it is more potent than irbesartan, as it...
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The elimination half-life and drug clearance of drugs following nonlinear kinetics can vary with dosage. The Michaelis-Menten parameters and drug concentration influence these factors. As the dose increases, the elimination half-life tends to lengthen, resulting in a reduction in clearance and a disproportionately larger area under the curve. The total clearance can be derived from the Michaelis-Menten equation for drugs following a one-compartment model.
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Chloroquine commonly induces hormetic dose responses.

Edward J Calabrese1, Jaap C Hanekamp2, Yannic N Hanekamp3

  • 1Department of Environmental Sciences, University of Massachusetts, Amherst, MA 01003, United States of America.

The Science of the Total Environment
|October 5, 2020
PubMed
Summary

Chloroquine, often studied for COVID-19, commonly induces hormetic effects. This biphasic dose response impacts diverse biological models, influencing cell types, viral replication, and neuroprotection, with clinical implications.

Keywords:
Biphasic dose responseCOVID-19ChloroquineDose-responseHormesisHydroxychloroquine

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Area of Science:

  • Pharmacology
  • Toxicology
  • Cell Biology

Background:

  • Chloroquine's use in COVID-19 treatment garnered significant attention.
  • This focus prompted an investigation into chloroquine's low-dose effects and potential hormetic responses.

Purpose of the Study:

  • To investigate the hormetic-biphasic dose response effects of chloroquine across diverse biological models.
  • To analyze the impact of chloroquine on various cellular and physiological endpoints at low doses.

Main Methods:

  • Literature review and analysis of studies investigating chloroquine's effects.
  • Assessment of chloroquine's impact on cell lines (tumor and non-tumor), viral replication, sperm motility, behavior, and neuroprotection.

Main Results:

  • Chloroquine commonly induced hormetic effects across numerous cell types and biological endpoints.
  • Observed effects included enhanced viral replication, sperm motility, and neuroprotection, alongside decreased convulsion risks.
  • Hormetic responses were noted in both tumor and non-tumor cell lines.

Conclusions:

  • Hormetic dose responses are a common occurrence with chloroquine treatment across a range of biological models.
  • Findings highlight the importance of dose selection in study design and clinical application.
  • Clinical concerns and opportunities arise depending on the specific biological endpoint considered.