Neurotransmitters Signaling Transmission

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Neurotransmitters / Signaling / Transmission

• Neuropsychopharmacology
• Classification of Drug Actions
• Neurotransmitters / Pathways
• Systems

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Classification of Drug Action

• Drug Dosage
• Lock-key method
• Routes of Administration
• Pharmacodynamics
• Pharmacokinetics

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History of Neuropsychopharmacology

• Recreational and Ritualistic Use of Drugs
• Acetylcholine
• Neuromuscular junction
• 1950s (chloropromazine)

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Drug Action - 1

• Binding affinity / Efficacy
• Agonist (high efficacy)
• Antagonist (low efficacy)
• Partial Agonist
• Competitive versus Non-competitive Agonist

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Drug Action - 2

• DRC
• ED50
• Maximum / Secondary binding
• Therapeutic index (ED50 / LD50)
• Tolerance
• Metabolic
• Functional

• Regulation (up- down-)
• Cross-tolerance
• Withdrawal
• Sensitization

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Drug Action - 3

• Administration
• Ingestion
• Inhalation (increases bioavailability)
• Injection (peripheral, central)
• Pharmacokinetics (ADME)
• Absorption
• Distribution
• Metabolism (biotransformation into inactive
  metabolites)
• Elimination

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Pharmacodynamics - Drug Action on Neurons

• Presynaptic events
• Axonal transport (e.g., colchicine)
• Storage of transmitters (e.g., reserpine)
• Blockage of vesicular release of transmitters
• Botulinum toxin (prevents release of ACh)
• Botox (temporary muscle paralysis)
• Neuromodulators (facilitate release of NTs)
• Caffeine blocks adenosine, increases release of
  DA
• Post-synaptic events
• Post-synaptic receptor blockage / activation
  (e.g., curare, ACh nicotinic antagonist)
• Prolonged activation (i.e., blockage of
  degradation enzyme)

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Neurotransmitters Criteria

• Presynaptic Neuron
• Synthesis Enzymes in Presynaptic Neuron
• AP-induced Release
• Postsynaptic Selective Receptors
• Exogenous Application
• Blockage of Release Impedes Action

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Neurotransmitters Examples

• Catecholamines
• Dopamine (DA)
• Epinephrine (E) / Adrenalin
• Norepinephrine (NE) / Noradrenaline
  Monoamines
• Indolamine
• Serotonin (5-hydroxytryptamine)
• (5-HT)
• Acetylcholine (ACh)

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Synthetic Pathways DA / NE / E
DA
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2
Tyrosine
L-Dopa
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Dopamine(DA)
Tyrosine hydroxylase
Dopamine ?- hydroxylase
Aromatic L-amino acid decarboxylase
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Norepinephrine (NE)
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Phenylethanolamine N-methyltransferase
NE
Epinephrine (E)
E
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Synthetic Pathways ACh
ACh
1
2
Acetyl CoA Choline
Acetylcholine (ACh)
Choline Acetyltransferase (ChAT)
Choline acetic acid
Acetylcholine (ACh)
Acetylcholinesterase (AChE)
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Take Home Message

• Drug Action
• Agonist / Antagonist
• DRC
• Tolerance (metabolic, functional)
• Monoamines and ACh
• Neurotransmitter Pathways