Neurotransmitters and Drug Action

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Neurotransmitters and Drug Action
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What is a Neurotransmitter?

• Neurotransmitters are chemical messengers that
  carry information from the presynaptic neuron to
  the postsynaptic neuron

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Transmission of Neurotransmitters

• W Receiving Neuron
• X Synaptic Cleft
• Y Terminal Button
• Z Neurotransmitters

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Transmission of Neurotransmitters

1. Synaptic vesicles fill with neurotransmitters
2. Neurotransmitters are released into the synaptic
   cleft
3. Neurotransmitters connect to receptor sites on
   the postsynaptic neuron

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Neurotransmitters

• Autoreceptors neurotransmitter receptors located
  on the presynaptic neuron
• They provide feedback on the amount of
  neurotransmitter in the synaptic cleft
• If levels are too high, they will cause a
  reduction in the release of the neurotransmitter

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Neurotransmitters

• Neuromodulators chemicals that affect the
  activity or release of a neurotransmitter
• They may make the release more or less effective
  at the postsynaptic cell
• They may effect the presynaptic cell by modifying
  the release of a neurotransmitter
• Effects may be long or short term
• Substances that act as neurotransmitters in one
  synapse may act as neuromodulators in another

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Neurotransmitters

• Dales Law the theory that neurons always
  produce the same neurotransmitter at each synapse
• This is usually true, but not always
• Some neurons release more than one chemical at a
  time
• When multiple chemicals are released, it is
  usually a neurotransmitter and a neuromodulator

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Neurotransmitters

• Neurotransmitters can be excitatory or inhibitory
• Excitatory neurotransmitter opens Na ion gate,
  allowing positive charge to flow in and
  depolarize the neuron
• Inhibitory neurotransmitter opens ion gates that
  either allow negative charge (Cl-) to flow in or
  positive charge (K) to flow out. This
  hyperpolarizes the neuron.

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Neurotransmitters

• There are more than 50 currently identified
  neurotransmitters, and there may be many more
• Types of neurotransmitters Include
• Acetylcholine
• Biogenic amines (monoamines)
• Amino acids
• Peptides
• Morphine like neurotransmitters

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Neurotransmitters

• Neurons are classified by the main
  neurotransmitter that they release. For example
• Cholinergic neurons release acetylcholine
• Dopaminergic neurons release dopamine
• Etc.

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Acetylcholine (Ach)

• Functions in both the Peripheral Nervous System
  (PNS) and Central Nervous System (CNS)
• PNS Activates muscles
• CNS Helps with anti-excitatory actions
• Also enhances sensory perceptions when we wake
  up, is an inducer of REM sleep, and helps to
  sustain attention

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Monoamines

• There are three categories of monoamines
• Catecholamines
• Serotonin
• Histamine

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Catecholamines

• Norepinephrine (NE)
• Also known as noradrenaline
• Works on sympathetic nervous system, helps to
  trigger fight-or-flight reactions.
• Increases heart rate, releasing glucose, and
  increases blood flow to skeletal muscles
• Epinephrine (E)
• Also known as adrenaline
• Works with norepinephrine to trigger
  fight-or-flight reactions
• Increases heart rate, constricts blood vessels,
  dilates air passages

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Catecholamines

• Dopamine (DA)
• Part of the brains reward system
• Released with rewarding experiences or substances
  (eating, sex, drug use, etc.)
• Involved in motivation, learning, and
  reward-seeking behavior

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Serotonin (5-HT)

• Often referred to as the happiness hormone
  (despite not being a hormone)
• Contributor to feelings of well-being
• Also regulates mood, muscle contractions,
  appetite, sleep
• Involved in memory and learning

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Amino Acids

• Not just found in neurons, serve metabolic and
  other biochemical functions as well
• Amino Acid neurotransmitters include
• Gamma-amniobutyric acid (GABA)
• Glycine
• Glutamate
• Proline

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Gamma-aminobutyric Acid (GABA)

• GABA is one of the major inhibitory
  neurotransmitters
• Works on chloride channels, allowing Cl to flow
  out of the cell

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Drugs

• Can be defined as any chemical substance that
  affects the processing of the mind or body

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Psychotherapeutic Drugs

• Anti-Depressants
• Monoamine oxidase inhibitors (MAOIs)
• Tricyclic anti-depressants (TCAs)
• Selective Serotonin Reuptake Inhibitors (SSRIs)
• Norepinephrine Reuptake Inhibitors (NARIs) and
  Serotonin Norepinephrine Reuptake Inhibitors
  (SNRIs)

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MAOIs

• Block the activity of monoamine oxidase
• Monoamine oxidase is an enzyme that destroys
  dopamine, norepinephrine, and serotonin
• Allows higher levels of these mood-regulating
  chemicals to exist in the synapse, and synaptic
  activity will increase

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TCAs

• Named after their 3-ringed chemical structure
• Can inhibit reuptake of serotonin and
  norepinephrine
• Can also antagonize production of serotonin and
  norepinephrine
• Negative side effect blocks transmission at
  cholinergic synapses causing side effects like
  dry mouth and blurry vision

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Reuptake Inhibitors

• SSRIs, NARIs and SNRIs
• Block presynaptic cells from reabsorbing
  serotonin, norepinephrine, or both
• This increases the amount of serotonin and/or
  norepinephrine in the synapse
• Increases firing of target neurons

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Antipsychotics

• Dopamine hypothesis theory that schizophrenia is
  the result of too much dopamine activity

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Typical Antipsychotics

• First antipsychotics available
• Blocked dopamine receptors
• Caused a vast array of nasty side effects,
  including parkinsons-like conditions

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Atypical antipsychotics

• Work by blocking specific dopamine subtypes
• These subtypes are not as present in the motor
  system
• Dopamine activity is lessened without as much
  physical damage

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Drugs

• Stimulants
• Opiates
• Hallucinogens

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Stimulants

• Primarily affect synapses that use serotonin,
  epinephrine, norepinephrine, and dopamine
• Cause transmitter to release randomly into
  synaptic cleft
• Increase amount of transmitter released during
  action potential
• Block reuptake of transmitter

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Opiates

• We have opioid receptors in the brain, and the
  body creates opioids naturally (also known as
  endorphins)
• The opioid activates the reward system
• Connects to opioid receptors in the reward system
• Releases increased dopamine, further activating
  the reward system

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Hallucinogens

• Block serotonin receptors in peripheral nervous
  system
• Antagonize serotonin receptors in central nervous
  system
• Affects Locus Coeruleus (LC) which sends sensory
  information to the cortex
• Increases sensitivity to novel experiences

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Questions?