Summary: New study reveals key biological process targeted by SSRIs, suggesting new clinical applications. The study found that SSRIs affect membrane trafficking in cells, which could explain their broader effects.
Remarkably, a single dose of fluvoxamine in mice allowed delivery of the drug across the blood-brain barrier. This discovery could lead to SSRIs making it easier to deliver drugs for conditions like dementia.
Highlights:
- SSRIs impact the ability of cells to transport materials via membrane trafficking.
- A single dose of fluvoxamine can facilitate drug delivery across the blood-brain barrier in mice.
- This finding suggests potential new uses of SSRIs in treating hard-to-reach diseases like dementia.
Source: King’s College London
Since the 1980s, selective serotonin reuptake inhibitor (SSRI) antidepressants have formed the backbone of treatment for depression and other mental health problems worldwide, with tens of millions of prescriptions annually alone. UK. Yet their mechanisms of action – and their broader effects on the entire body – are not yet fully understood.
Today, a study by King researchers was published in Molecular Psychiatryidentifying a key biological process targeted by SSRIs and proposing the use of these drugs in novel clinical applications.
In this work, all currently prescribed SSRIs were tested on different cell types grown in petri dishes, using drug concentrations similar to those found in the blood of patients treated for depression. Unexpectedly, almost all antidepressants affected the ability of cells to transport material in and out of their environment through a process called membrane trafficking.
Additionally, a single injection of the antidepressant fluvoxamine in mice allowed a fluorescent compound that would normally stay outside the brain to accumulate inside the brain, crossing the cellular barrier separating the brain from the rest of the brain. body.
Dr Oleg Glebov, from King’s IoPPN, said: “Given how little is known about the wider effects of antidepressants, we wanted to find out more about how these drugs affect the cells in our brain and body. We found that most antidepressants regulate the same key biological process in many tissues, which probably has little to do with their effect on depression.
“Additionally, our data suggest that a single dose of an antidepressant may be sufficient to effectively open the blood-brain barrier for the delivery of other medications. We hope this discovery can help improve the clinical effectiveness and reduce the treatment cost of new dementia drugs, which are currently not available to the millions of people who need them.
“In addition, we are excited to explore whether antidepressants can help deliver medications to other hard-to-reach parts of the body.”
Exactly how SSRIs control membrane trafficking remains unclear, and uncovering the intricacies at the molecular level will require collaboration across multiple scientific disciplines. Likewise, it will be necessary to determine in the clinic whether SSRIs are truly effective for administering other medications in humans.
Still, it’s entirely possible that this study marks the start of a whole new career for these venerable, 30-plus-year-old drugs, this time helping other drugs do their jobs.
About this neuropharmacology research news
Author: Oleg Glebov
Source: King’s College London
Contact: Oleg Glebov – King’s College London
Picture: Image is credited to Neuroscience News
Original research: Free access.
“Antidepressant-induced membrane trafficking regulates blood-brain barrier permeability” by Oleg Glebov et al. Molecular Psychiatry
Abstract
Antidepressant-induced membrane trafficking regulates blood-brain barrier permeability
As the most prescribed psychotropic medications in current medical practice, antidepressants (ADs) of the selective serotonin reuptake inhibitor (SSRI) class represent prime candidates for drug repurposing. However, the mechanisms underlying their mode of action remain unclear.
Here we show that common SSRIs and some representatives of other AD classes bidirectionally regulate liquid-phase absorption at therapeutic and lower concentrations.
We further characterize membrane trafficking induced by a canonical SSRI fluvoxamine to show that it involves enhancement of clathrin-mediated endocytosis, the endosomal system, and exocytosis. RNA sequencing analysis showed few differences associated with fluvoxamine, consistent with the effect being independent of gene expression.
Fluvoxamine-induced increase in membrane trafficking stimulated transcytosis in blood-brain barrier cellular models, while a single injection of fluvoxamine was sufficient to allow brain accumulation of a fluid-phase fluorescent tracer in vivo .
These results reveal modulation of membrane trafficking by DAs as a possible cellular mechanism of action and indicate their potential for clinical repositioning to regulate drug delivery to the brain.
News Source : neurosciencenews.com
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