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Prozac

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Nicholas Spittle

on 28 April 2010

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Transcript of Prozac

Prozac History History of Antidepressants (ADs)

Opiates & amphetamines used until 1950's

In 1951, Irving Selikoff and Edward Robitzek tested anti-tuberculosis agents isoniazid and iproniazid

Saw no improvement with TB, but saw patients' moods improve

Mechanism was unknown, called a "Psycic Energizer"

Widely used, but recalled after its effect on liver was discovered
History of Antidepressants
Roland Kuhn discovered effect of tricyclic compounds as AD

Kuhn discovered "G 22355". a compound that showed positive effects on depression

Led to production of first tricyclic AD, Imipramine SSRI's
Though imipramine showed positive effects, not extremely popular

Indalpine was the first SSRI
SSRI's
SSRI = selective serotonin reuptake inhibitor

Indalpine, first sold in 1983

Found to cause neutropenia, lowering of the white blood cell count Prozac
Discovered by Eli Lilly Company in 1972

Approved by FDA in 1986

Chemical Name: Fluoxetine Hydrochloride

Marketed relentlessly by Eli Lilly

Most widely prescribed AD to date

Low Side Effects & Reactions with other drugs

Mechanism Sources
1. "The Invention of Prozac", http://inventors.about.com/library/weekly/aa980225.htm
2. Lieberman III,Joseph A. "History of the Use of Antidepressants in Primary Care",Primary Care Companion J Clin Psychiatry 2003;5 (suppl 7) .
3. "Serotonin" Health Scout Network, http://www.healthscout.com/ency/68/409/main.html
4. "Top 200 Drugs of 2008" Pharmacy Times, http://www.pharmacytimes.com/issue/pharmacy/2009/2009-05/RxFocusTop200Drugs-0509.
5. PubChem.com (chemical structures)
6. "Drugs in the Nervous System" http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/D/Drugs.html
7.Wong D, Horng J, Bymaster F, Hauser K, Molloy B (1974). "A selective inhibitor of serotonin uptake: Lilly 110140, 3-(p-trifluoromethylphenoxy)-N-methyl-3-phenylpropylamine". Life Sci 15 (3): 4719. doi:10.1016/0024-3205(74)90345-2. PMID 4549929.

Serotonin
Neurotransmitter that relays messages between neurons

Neurons communicate across synapses via neurotransmitters

Influences function of cardiovascular, renal, immune, and gastrointestinal systems.

Altered levels cause: schizophrenia, depression, compulsive disorders (OCD) as well as learning problems.

Low Levels = Depression



Serotonin directly effects anxiety mechanisms and
regulation of
mood & thoughts
aggression
appetite
sex drive,
sleep cycle. Cultural Impact In 2008,
$23,271,000 in Fluoxetine prescriptions

Third more perscribed antidepressant (Zoloft)

Improved the lives of millions with depression

Neurotransmitter Release

Action Potential causes inward flow of Ca ions (Voltage Gated Ion Channels)

Calcium ions trigger release of neurotransmitters at synaptic bulb

Reuptake of Neurotransmitters

Neurotransmitters stored in vesicles by vesicle transporters (Active Transport, H+)





Types of Antidepressants

Selective Serotonin Reuptake Inhibitors (SSRIs)

Serotonin Norepinephrine Reuptake Inhibitors (SNRIs)

Norepinephrine Reuptake Inhibitors (NRIs)

Norepinephrine-Dopamine Reuptake Inhibitors (NDRIs)

Selective Serotonin Reuptake Enhancers (SSREs)

Tricyclic Antidepressants (TCAs)
TCAs were the first used (imipramine)

The Most Common and Commercially Available Antidepressants are SSRIs
These Include…
Citalopram (Celexa)
Escitalopram (Lexapro)
Fluvoxamine (Luvox)
Paroxetine (Paxil)
Sertraline (Zoloft)

And of course, Fluoxetine
Which is everyone’s favorite…
Prozac

Prozac must first be metabolized and activated…

Fluoxeine is metabolized in the liver by the cytochrome p450 isoenzyme CYP2D6, shown as follows: CYP2D6 converts the drug into its active metabolite called norfluoxetine shown below:
Remember, A neuron gap looks like this…

Prozac has two main functions:
The Primary Function:
1. Serotonin (the neurotransmitter of interest) is released from the sending cell

2. Not all of the serotonin can be absorbed immediately

3.The leftover serotonin is reabsorbed by the uptake pump of the sending cell

4.Prozac blocks this pump, allowing for the receptors to be exposed to serotonin for a longer amount of time, in turn allowing for more serotonin to be absorbed by the receptors


The Secondary Function:

Prozac blocks the sensor on the axon that tells the cell when enough serotonin has been produced, causing an overproduction of the neurotransmitter

Side Effects Insomnia

Loss of Appetite

Weakness

Possible increase in thoughts of suicide beginning of treatment Questions? Logan Pry & Nick Spittle
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