Is the bell-shaped dose-response curve of the selective serotonin reuptake inhibitor due to 5-HT auto-receptors?

08:00 EDT 16th March 2020 | BioPortfolio

Summary of "Is the bell-shaped dose-response curve of the selective serotonin reuptake inhibitor due to 5-HT auto-receptors?"

A dose-response curve is a plot of drug efficacy versus dose. Interestingly, some antidepressants show a bell-shaped dose-response curve where increasing dose leads to increasing efficacy only up to a point, whereupon further increases lead to decreasing efficacy. Here, we propose that the first part of the curve reflects the basic, uncomplicated dose-response relationship of these antidepressants whereas the second, decreasing part remains to be explained. Our hypothesis is that a negative feedback pathway through 5-HT auto-receptors decreases the efficacy of selective serotonin reuptake inhibitors with increasing dose, thereby creating the second, anomalous part of the dose-response curve. This effect can also account for the so-called therapeutic window of such antidepressants.


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Name: Medical hypotheses
ISSN: 1532-2777
Pages: 109681


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Medical and Biotech [MESH] Definitions

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A statistical means of summarizing information from a series of measurements on one individual. It is frequently used in clinical pharmacology where the AUC from serum levels can be interpreted as the total uptake of whatever has been administered. As a plot of the concentration of a drug against time, after a single dose of medicine, producing a standard shape curve, it is a means of comparing the bioavailability of the same drug made by different companies. (From Winslade, Dictionary of Clinical Research, 1992)

Sodium chloride-dependent neurotransmitter symporters located primarily on the PLASMA MEMBRANE of serotonergic neurons. They are different than SEROTONIN RECEPTORS, which signal cellular responses to SEROTONIN. They remove SEROTONIN from the EXTRACELLULAR SPACE by high affinity reuptake into PRESYNAPTIC TERMINALS. Regulates signal amplitude and duration at serotonergic synapses and is the site of action of the SEROTONIN UPTAKE INHIBITORS.

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