Neurotransmitters and Pharmacology

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Neurotransmitters and Pharmacology

• Mindy M. Escobar
• Argyle V. Bumanglag
• September 20, 2007

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Neurotransmission
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Why is it important to regulate the amount of
neurotransmitter present in the synapse?
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Serotonin

• Plays an important role in regulation of
• Aggression Appetite
• Body temperature Sleep
• Vomiting Mood
• Sexuality Anger

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Principle source of serotonin
Raphe nuclei
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Serotonin receptor distribution
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Serotonergic Synapse
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Psychedelic serotonin modulation
Mood, thought processes and concentration
Appetite
Psychomotor control and perception
Emotional responses
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Hallucinogens (LSD)

• Serotonin antagonist
• Completely blocks activity of Raphe nuclei
• Results in disinhibition of critical control
  systems over sensation, sleep, attention, and mood

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MDMA (ecstasy)

• Increases serotonin release and blocks reuptake
• Enhances communication, reduces psychological
  defenses, and increases capacity for
  introspection
• Significant risk for chronic physical harm

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Therapeutic serotonin modulation
www.psychiatrist.com/pcc/brainstorm/br6305.htm
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Tricyclics
Examples Vivactil, Elavil, Norpramin, Asendin,
Anafranil
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SSRIs
Examples Prozac, Paxil, Zoloft, Lexapro, Celexa
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Dopamine Synthesis Pathway
(1)
Pre-synaptic DA neuron
(2)
(3)
(6)
DA Transporter
(4)
(5)
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Dopamine Receptors

• All DA receptors are G-protein-coupled
  metabotropic receptors
• There are 5 subtypes of dopamine (DA) receptors
  that can be grouped into 2 main classes D1 and
  D2 receptors
• D1 receptors include subtypes D1 and D5
• D1 receptors are the most abundant and widespread
  in areas receiving DA innervation
• D1 receptors mediate peripheral effects - renal
  vasodilatation and increased myocardial
  contractility
• D2 receptors include D2,D3, and D4
• Antipsychotic drugs show a high affinity for the
  D2 receptors, which may play a role in
  schizophrenia
• D3 receptors found on the presynaptic terminal
  act to inhibit DA synthesis and release

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Dopamine Pathways
3 Major Pathways in the CNS

• (1) Nigrostriatal system
• Motor control
• (2) Mesolimbic/mesocortical pathway
• Behavioral effects
• (3) Tuberohypophyseal system
• Endocrine control

(2)
(1)
(3)
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Cocaine

• Derived from the leaves of the coca plant, which
  grows in some South American Countries
• One of the major psychostimulants of abuse
• Mechanisms of Action
• produces massive release of dopamine into the
  synaptic cleft
• blocks the neuronal re-uptake transport system
  for catecholamines (DA, NE, 5-HT)
• euphoric effects are due to its effects on DA
• Other uses
• medical use as a local anesthetic

Coca plant
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Cocaine Mechanisms of Action
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Cocaine Effects

• Psychomotor effects (DA mediated)
• Euphoria
• Increased motor activity
• Magnification of pleasure
• Peripheral effects
• Tachycardia
• Vasoconstriction
• Increased blood pressure
• Adverse effects
• Hypertension
• Vasospasm of arteries
• Myocardial infarcts
• Stroke
• Impaired brain development in utero
• High risk for dependency

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Dopamine Reward Pathways
http//thebrain.mcgill.ca
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Parkinsons Disease

• Parkinsons Disease is a chronic movement
  disorder first described in 1817 by James
  Parkinson
• It typically starts around the age of 60,
  although 5-10 exhibit signs before the age of 40
• Clinical symptoms
• Usually begins with a slight tremor or stiffness
  involving an arm or leg on one side of the body
• Prominent tremor at rest and occurs at a
  frequency of 3-6 per second
• Pill rolling
• Limb rigidity
• Akinesia
• Bradykinesia
• Characteristic gait, drooling, eye blinking, and
  a frozen facial expression

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Parkinsons Disease

• Clinical manifestations are caused by a network
  dysfunction of the basal ganglia
• In the normal brain, DA projections from the
  substantia nigra maintain normal function in
  basal ganglia
• Degeneration of DA neurons in the substantia
  nigra removes a DA-mediated inhibition that makes
  normal movement possible
• Clinical signs begin when approximately 40 of
  DA neurons have died and approximately 50 of the
  DA in axon terminals of the basal ganglia has
  been depleted

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Anatomy of the Basal Ganglia
www.dana.org
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Parkinsons Disease
http//www.urmc.rochester.edu/neuroslides/slide199
.html
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Treatment of Parkinsons Disease

• Goal of therapy
• Restore the deficit in DA receptor function
• Inhibit muscarinic cholinergic receptors
• Drugs used in treatment of Parkinsons Disease
• Levodopa
• Most widely used form of therapy for Parkinsons
  Disease
• Converted to DA, thereby restoring concentration
  of DA at the basal ganglia
• DA receptor agonists
• Mimics the effects of endogenous dopamine
• Less effective than levodopa
• Monoamine (MAO) inhibitors
• Inhibition of MAO increases DA concentration
  within cells and at the postsynaptic receptor
• Muscarinic cholinergic receptor antagonists
• Affect the tremor more than the rigidity and
  hypokinesia
• Amantidine
• Antiviral drug that was accidentally found to
  have anti-PD effects
• Mechanism uncertain but probably increases
  endogenous DA