Topics

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.

Affiliation

Journal Details

This article was published in the following journal.

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

Links

DeepDyve research library

PubMed Articles [16893 Associated PubMed Articles listed on BioPortfolio]

5-HT agonist, lorcaserin, reduces aggressive responding in intermittent explosive disorder: A pilot study.

Impulsive aggressive behavior is associated with reduced central function of serotonin (5-HT). Although selective serotonin reuptake inhibitors can reduce such behaviors, many with history of impulsiv...

Recent Advances in Liquid Chromatographic Methods for the Determination of Selective Serotonin Reuptake Inhibitors (SSRI) and Serotonin Norepinephrine Reuptake Inhibitors (SNRI).

Depression is now the second largest public health burden throughout the world. Selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) have replaced o...

Dual roles for the TSPYL family in mediating serotonin transport and the metabolism of selective serotonin reuptake inhibitors in MDD patients.

We previously reported that TSPYLs are transcription regulators for CYP3A4, CYP2C9 and CYP2C19. Here, we observed dual roles for TSPYLs in mediating serotonin transport and the metabolism of selective...

Electrophysiological characterization of a novel AMPA receptor potentiator, TAK-137, in rat hippocampal neurons.

We have recently discovered an alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA-R) potentiator TAK-137, 9-(4-phenoxyphenyl)-3,4-dihydropyrido[2,1-c][1,2,4] thiadiazine 2,2-dioxi...

Selective Serotonin Reuptake Inhibitor Use and Hip Fracture Risk Among Patients on Hemodialysis.

Use of selective serotonin reuptake inhibitors (SSRIs) has been associated with hip fracture risk in the general population. This study examined this relationship among patients with kidney failure tr...

Clinical Trials [12343 Associated Clinical Trials listed on BioPortfolio]

Antidepressant Safety in Kids Study

This study will evaluate the risks and benefits of treatment with a selective serotonin reuptake inhibitor or serotonin-norepinephrine reuptake inhibitor in children and adolescents with a...

12 Week Safety Trial of Flibanserin in Depressed Women Taking a Selective Serotonin Reuptake Inhibitor or Norepinephrine Serotonin Reuptake Inhibitor With Decreased Sexual Desire and Distress

The current trial will explore the safety of flibanserin in combination with Selective Serotonin Reuptake Inhibitors or Norepinephrine Serotonin Reuptake Inhibitors in a representative pop...

Dose-finding Study of Selective Serotonin Reuptake Inhibitors to Enhance Neuroplasticity

The brain is able to change throughout life in response to learning, or injury, or to adapt to changes in the environment, which is known as neuroplasticity. Stroke survivors suffer disabl...

Does Vilazodone Help With Antidepressant-associated Sexual Dysfunction?

This is a three-center, randomized, double-blind, fixed dose study designed to assess the efficacy, safety, and tolerability of a switch to vilazodone for sexual dysfunction associated wit...

A Study to Compare the Efficacy, Safety, and Tolerability of JNJ-42847922 Versus Quetiapine Extended-Release as Adjunctive Therapy to Antidepressants in Adult Participants With Major Depressive Disorder Who Have Responded Inadequately to Antidepressant Th

The purpose of this study is to assess the efficacy of flexibly dosed JNJ-42847922 (20 milligram [mg] or 40 mg) compared to flexibly dosed quetiapine extended-release (XR) (150 mg or 300 m...

Medical and Biotech [MESH] Definitions

An adverse drug interaction characterized by altered mental status, autonomic dysfunction, and neuromuscular abnormalities. It is most frequently caused by use of both serotonin reuptake inhibitors and monoamine oxidase inhibitors, leading to excess serotonin availability in the CNS at the serotonin 1A receptor.

A selective serotonin reuptake inhibitor. It is effective in the treatment of depression, obsessive-compulsive disorders, anxiety, panic disorders, and alcohol amnestic disorders.

Compounds that specifically inhibit the reuptake of serotonin in the brain. This increases the serotonin concentration in the synaptic cleft which then activates serotonin receptors to a greater extent. These agents have been used in treatment of depression, panic disorder, obsessive-compulsive behavior, and alcoholism, as analgesics, and to treat obesity and bulimia. Many of the ADRENERGIC UPTAKE INHIBITORS also inhibit serotonin uptake; they are not included here.

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.

Quick Search


DeepDyve research library

Relevant Topics

Selective serotonin reuptake inhibitors SSRIs
Serotonin and norepinephrine reuptake inhibitors (SNRIs) are a class of medications that are effective at easing depression symptoms. SNRIs are also sometimes used to treat other conditions such as anxiety and nerve pain. How SNRIs work Serotonin (se...

Drug Discovery
Clinical Approvals Clinical Trials Drug Approvals Drug Delivery Drug Discovery Generics Drugs Prescription Drugs In the fields of medicine, biotechnology and pharmacology, drug discovery is the process by which drugs are dis...


Searches Linking to this Article