MadSci Network: Neuroscience
Query:

Re: What are Selective Serotonin reuptake inhibitors and how do they work?

Date: Fri Jun 2 12:19:55 2000
Posted By: Kevin Caldwell, Faculty, Neurosciences, University of New Mexico
Area of science: Neuroscience
ID: 958697812.Ns
Message:

 
Great question!


Serotonin which is present in the extracellular (i.e., outside of a cell) 
space is actively transported into a cell.  The process of taking the 
serotonin back into the cell is termed "reuptake".  There are different 
reuptake mechanisms, or transporters, for different neurotransmitters- for 
example, serotonin and norepinephrine, which is also a neurotransmitter in 
the central nervous system, are transported by different proteins. 
Therefore, selective serotonin reuptake inhibitors (SSRIs) selectively 
inhibit the reuptake of serotonin.  SSRIs are used clinically to treat 
depression.  Drugs termed tricyclic antidepressants inhibit the reuptake of 
norepinephrine.  These drugs are also used clinically as antidepressants.  
Both SSRIs and tricyclic antidepressants are described in standard 
pharmacology textbook, such as, Goodman & Gilman's "The Pharmacological 
Basis of Therapeutics"

Tests to determine if a drug is an SSRI employ microdialysis.  In this 
procedure a fluid is passed through a tissue (either in vivo using an 
immobilized animal or in vitro using an excised tissue).  As the fluid 
passes through the tissue it "washes-out" chemicals that are not inside or 
bound to cells.  The solution is collected after leaving the tissue and is 
analyzed to determine its components.  A drug, such as an SSRI, can be 
added to the solution so that the tissue is exposed to the drug.  In order 
to determine if a drug blocks serotonin reuptake it is applied to a tissue 
and the amount of serotonin that is present in the collected material is 
determined.  In the case of a drug that blocks serotonin reuptake, the 
amount of serotonin that is present in the extracellular space will be 
increased, so more serotonin is available to be "washed out" of the tissue 
and, therefore, will be collected from the tissue.  In order to determine 
if the drug selectively blocks serotonin reuptake, the solution is also 
analyzed for other neurotransmitters, such as norepinephrine. 

Here are references to a couple of recent scientific studes that employed 
microdialysis.
1 Dawson, L.A., & Nguyen, H.Q. (2000) The role of 5-HT(1A) and 5-HT(1B/1D) 
receptors on the modulation of acute fluoxetine-induced changes in 
extracellular 5-HT: the mechanism of action of (+/-)pindolol.  
Neuropharmacology, Vol. 39, pp. 1044-52

2 Cui, M., Feng, Y., McAdoo, D.J., & Willis, W.D.  (1999) Periaqueductal 
Gray Stimulation-Induced Inhibition of Nociceptive Dorsal Horn Neurons in 
Rats Is Associated with the Release of Norepinephrine, Serotonin, and Amino 
Acids.  The Journal of Pharmacology and Experimental Therapeutics, Vol. 
289, pp. 868-876,





Current Queue | Current Queue for Neuroscience | Neuroscience archives

Try the links in the MadSci Library for more information on Neuroscience.



MadSci Home | Information | Search | Random Knowledge Generator | MadSci Archives | Mad Library | MAD Labs | MAD FAQs | Ask a ? | Join Us! | Help Support MadSci


MadSci Network, webadmin@www.madsci.org
© 1995-2000. All rights reserved.