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Serotonin and IBS
From the Winter 2000 issue of
Participate
How do
the new serotonergically active drugs currently being developed for the
treatment of irritable bowel syndrome (IBS) differ from the selective
serotonin reuptake inhibitor (SSRI) class of drugs [e.g., fluoxetine
(Prozac), paroxetine (Paxil), sertraline (Zoloft)]? The SSRIs have been
specifically developed as antidepressant drugs. Serotonin is found in both
the brain and the gut, but it is now widely understood that 95% of the
serotonin in the body resides in the gut.
There are different types
of serotonin that are called receptor subtypes, identified as "5-HT"
followed by a number. The serotonin found in the gut consists mainly of
5-HT3 and 5-HT4 subtypes. Most of the serotonin found in the brain is of
the 5-HT1 and 5-HT2 subtypes; antidepressants tend to work on these
subtypes. Nevertheless, they also have some effect on the 5-HT3 and 5-HT4
receptors located mainly in the gut. This effect may explain, in part, why
antidepressants can help relieve some IBS symptoms.
The newer
serotonergically active drugs for treatment of IBS target the serotonin
found in the gut. They are not antidepressants and have their major effect
on the 5-HT receptors in the gut, not the brain.
The newer drugs
for treatment of IBS, such as alosetron and tegaserod (which is not yet
available for use), target 5-HT3 and 5-HT4 respectively. These drugs are
"gut specific" and tend to have minimal effect on brain serotonin. They
are not antidepressants. However, these new gut specific drugs and
antidepressants will, no doubt, be used in a complementary manner to treat
IBS.
5-HT, Receptors, and IBS --
From the
Fall 1999 issue of Participate
Serotonin (5-hydroxytryptamine, or 5-HT) is a chemical
neurotransmitter (a chemical in the nervous system that helps transmit
messages along the nervous system). It is found in three main areas of the
body: the intestinal wall, blood vessels, and the central nervous
system.
Chemical neurotransmitters produce their effects as a
consequence of interactions with appropriate receptors. In cell biology, a
receptor is a structure on the surface of a cell or inside a cell that
selectively receives and binds a specific substance -- such as a hormone
or a neurotransmitter.
Serotonin (5-HT) interacts with an array of
receptors. Approximately 14 types of serotonin receptors have been
identified in humans. These receptor sites are numbered. (For example,
serotonin receptor site 1 is labeled 5-HT1, site 2 is 5-HT2, etc.) These
different receptors act on different areas of the body, such as those
affecting smooth muscle relaxation, sleep regulation, cardiovascular
function, and gastrointestinal and vascular smooth muscle
contraction.
An antagonist acts against and blocks an action. An
agonist acts like and stimulates an action. Antagonists and agonists are
key agents in the chemistry of the human body and in pharmacology-the
study and development of drugs.
The new generation of drugs being
evaluated to treat IBS either block or stimulate the action of serotonin
at specific receptor sites that affect the GI tract.
For information, contact IFFGD