Journal about antidepressant drug
University number: 42904118
Date: 6 – 4 - 2012
Introduction:
In this journal I will talk about antidepressants drug which is the most
prescribed therapy for depression, also I'll explain how do antidepressants
work in the brain. I will show you the classification of antidepressants
and their use in treat a variety of psychiatric conditions, including mental
depression, social phobia, and mood, panic, or obsessive-compulsive
disorders, as well as other conditions. And i will reflected upon the most
important aspects and the role of medicinal chemistry studies in the
development of these agents.
body
An antidepressant is a medication used primarily in the treatment of
clinical depression. Some examples of antidepressants on the market
today are Prozac, Zoloft, Effexor, and Celexa. They also are not thought
to produce tolerance, although sudden withdrawal may produce adverse
effects. Antidepressants create little if any immediate change in mood and
require between several days and several weeks to take effect.
How Do Antidepressants Work in the Brain?
Antidepressants are believed to work by
helping the brain's neurotransmitters,
which are needed for normal brain
function and help control the mood and
functions in thinking, sleeping, eating,
response to pain and other actions.
Because they have to work at various
tasks within the body, antidepressant
medication slows down their removal or
helps to increase the levels of these
neurotransmitters in the brain. This
restores the brain's chemical balance to
help relieve symptoms of depression.
Chemicals in the brain can return normal function to people suffering
from extreme sadness, hopelessness and lack of interest in life, ill effects
experienced by people with depression. The work of antidepressants has
also been successful in the treatment of people with eating disorders,
chronic pain and other disorders that often carry depression with them.
classification of antidepressants
Monoamine Oxidase Inhibitors:
Monoamine oxidase inhibitors (MAOIs) are one of the oldest classes of
antidepressants and are typically used when other antidepressants have
not been effective. MAOIs prevent monoamine oxidase from breaking
down the monoamines. This results in an increased amount of active
monoamines in the brain.
They are used less frequently because they often interact with certain
foods and require strict dietary restrictions. MAOIs can also result in
severe adverse reactions if taken with many other medicines, including
some over-the-counter cough and cold remedies. MAOIs are mostly used
for atypical depression.
A newer type of MAOI called moclobemide is slightly different to the
older MAOIs. It is considered to be a safer choice than the older MAOIs,
as it requires fewer dietary restrictions and has fewer significant
interactions with other medicines. Moclobemide is considered a secondline treatment for major depression.
Tricyclic Antidepressants :
The tricyclic antidepressants are the most effective drugs presently
available for the treatment of depression. These act by block the
absorption (reuptake) of the neurotransmitters serotonin and
norepinephrine, making more of these chemicals available in the brain.
This seems to help brain cells send and receive messages. These
antidepressants also affect other chemical messengers, which can lead
to a number of side effects.
SAR
•Antidepressants are characterized by lack of co-planarity in the tricyclic
ring.
• Various side chains are noted in the entire class of antidepressants that
represent substituted ethyl and propyl amines.
• the N-monomethyl derivatives are more potent and have a more
rapid onset of activity than the corresponding N-disubstituted
compounds.
So we can increase the efficacy of some compound by convert Ndisubstituted to N-monomethyl derivatives.
• Marked activity is observed for secondary methylamino derivative,
while ethyl and propyl derivatives are less potent.
• Tertiary amine antidepressants like imipramine are more effective
inhibitors of serotonin uptake, useful in-patients with psychomotor
agitation. Secondary amines like protriptyline are more effective
inhibitors for nor-epinephrine uptake, useful in retarded depression,
owing to a lower sedation and hypotension.
So we can convert a compound from selective nor-epinephrine
reuptake inhibitor to selective serotonin reuptake inhibitors and vice
versa .
Products :
Aryl and aryloxyalkyl amine:
Fluoxetine ( Prozac), paroxetine ( seroxat) , Sertraline ( Zoloft)
Fluoxetine:
Fluoxetine is in a class of medications called selective serotonin
reuptake inhibitors (SSRIs). It works by increasing the amount of
serotonin, a natural substance in the brain that helps maintain mental
balance. it is used to treat depression, obsessive-compulsive disorder ,
some eating disorders, and panic attacks. Also it used to relieve the
symptoms of premenstrual dysphoric disorder, including mood swings,
irritability, bloating, and breast tenderness.
Selective norepinephrine uptake inhibitors:
It is a type of drug that acts as a reuptake inhibitor for the
neurotransmitters norepinephrine (noradrenaline) and epinephrine
(adrenaline) by blocking the action of the norepinephrine transporter
(NET). This in turn leads to increased extracellular concentrations of
norepinephrine and epinephrine and therefore an increase in adrenergic
neurotransmission.
Nisoxetine
Reboxetine
Bupropion
Selective serotonin uptake inhibitor and 5HT2A antagonist:
trazodone hydrochloride.
Trazodone also has anxiolytic and hypnotic
effects. Trazodone has considerably less
prominent anticholinergic (dry mouth,
constipation, tachycardia) and sexual side effects
than most of the tricyclic antidepressants (TCAs)
5HT1A agonist and partial agonist:
Buspirone
Alpha 2 Antagonists:
Mirtazapine
Conclusion:
Antidepressant drugs potentiate ether directly or indirectly the action of
norepinephrine and / or serotonin in the brain. This, along with other
evidence, led to biogenic amine theory, which proposes that depression is
due to a deficiency of monoamines, such as norepinephrine and serotonin
at certain key sites in the brain. After study SAR of antidepressant drugs
we succeeded to increase the selectivity and reduce side effect in some
compounds by modulation their structure for example: tertiary amine
antidepressants more selective to serotonin uptake, while Secondary
amines are more effective inhibitors for nor-epinephrine uptake and more
useful due to less sedating and hypotensive effects.