Summary of Synaptic Transmission

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Summary of Synaptic Transmission

• Neurons communicate with neurons thru synapse
• Transmitter (T) released at pre-synaptic membrane
• T diffuses across synapse and binds to receptor
  at post-synaptic membrane
• TR complex activates neuron (or other cell)
• T either destroyed by enzyme, or up-take mechanism

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Synapse
Psycho-Active Drug Targets?
Impulse
R
R
T
T
Impulse
T
T
R
T
Neuronal axon
T
(or activation Of non-neural Target cell)

R
T
T
R
Enzyme
T destroyed by enzyme or removed by
re-uptake
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Psycho-Active Drug Targets?
What components of the synapse Would you control
when you know An imbalance in transmitter
causes Behavioral changes?
Case Study of Serotonin and Depression
Many clinical depressions caused by low serotonin
levels
What drug options do we have?
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Serotonin Depression Five Options

• 1. Increase or decrease synthesis of T (e.g.,
  daylight increases T by inhibiting synthesis of
  melatonin out of balance in jet lag and SAD
  (seasonal affected disorder)
• 2. Provide precursors to T (e.g., amino acid
  tryptophan increases synthesis of T behavioral
  changes with tryptophan-containing foods, e.g.,
  bananas)

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Options Cont

• 3. Increase or decrease the release of T (e.g.,
  many drugs act this way, including some of the
  hallucinogens)
• 4. Block the receptor of T (e.g., many drugs act
  this way to reduce TR formation)
• 5. Block the enzyme destruction or re-uptake of T
  (e.g., action of Prozac) T stays in synapse
  longer time

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Viagra Story Another Example of Option 5

• Viagra Popular drug used to treat impotence or
  erectile dysfunction
• Normal male erection depends on cascade of events
  leading to relaxation of blood vessels to the
  penis
• Viagra works to extend the life-span of T
  involved in the relaxation process (not unlike
  the action of Prozac)

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Action of Viagra
Blood flow
Cascade of events 1.sensory stimulation 2.hypotha
lamus 3.autonomic stimulation of vessel
smooth muscle 4.Release of nitrous
oxide 5.activation of enzyme which converts
GTP to cGMP 6.cGMP relaxes muscle of blood
vessels (erection) 7.cGMP destroyed by esterase
enzyme (PROZAC INHIBITS THIS ENZYME)
arousal
erection
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Parkinsons Disease

• Neuro-degenerative disorder caused by loss of
  dopamine-producing neurons
• Symptoms tremors weakness loss of balance
  speech/swallowing trouble and other symptoms
  including immobilization, double vision, and
  depression
• Treatments are not permanent

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Treatments

• 1. Focus on tremors (e.g., drugs,
  electro-stimulation, and micro-surgery)
• 2. Treated depleted dopamine status with L-dopa
  (chemically similar to dopamine)
• Effects of L-dopa may only last 4-10 years
• Future options? Stem cell research
• Stem cells potentially useful to treat heart
  disease, diabetes, immune neuro-muscular disease

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Embryonic Stem Cells
Zygote 2-cell 4-cell
morula
Ectoderm Mesoderm Endoderm
blastocyst
Trilaminar embryo
Adult tissues
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Parkinsons Case Study

• Mother with Parkinsons disease is faced with
  treatment options from her grown children what
  is she to do?
• Read details at http//ublib.buffalo.edu/librari
  es/projects/
• Cases/fetal_tissue.html (by Fourtner, Fourtner
  and Herreid)
• What are the issues in the case study?

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Issues?

• Source of stem cells?
• How will treatment be implemented?
• Is procedure legal?
• Age of the donor cells?
• Fresh or stored cells to be used?
• Immune-suppression necessary?
• What have animal studies shown?