Neurotransmitter

• Neurotransmitter release


  1. Neurotransmitters are stored in synaptic vesicles

  2. Vesicles are transported to the presynaptic membrane

  3. Chemicals are released
• Transporter molecules


  Responsible for reuptake of neurotransmitter into a terminal
• Neurotransmitter storage


  Transporter molecules pump neurotransmitter molecules across the membrane, filling the vesicles
• Transporter molecules


  • Some can be blocked by a drug
  • Drug molecules bind to a particular site on the transporter and inactivate it
• Synaptic vesicles remain empty


  Nothing is released when the vesicles eventually rupture against the presynaptic membrane
• Antagonist drug action


  1. Prevents release of neurotransmitters from the terminal button

  2. Deactivates the proteins that cause synaptic vesicles to fuse with the presynaptic membrane and expel their contents
• Agonist drug action


  Binds with the proteins and directly triggers release of the neurotransmitter
• Types of drug action

  • Drug serves as precursor
  • Drug inactivates synthetic enzyme; inhibits synthesis of NT
  • Drug prevents storage of NT in vesicles
  • Drug stimulates release of NT
  • Drug inhibits release of NT
  • Drug stimulates postsynaptic receptors
  • Drug blocks post synaptic receptors
  • Drug stimulates autoreceptors; increases synthesis/release of NT
  • Drug blocks autoreceptors; increases synthesis/release of NT
  • Drug blocks reuptake
  • Drug inactivates acetylcholinesterase
• Postsynaptic receptors


  Neurotransmitter must stimulate them once released
• Direct agonist


  Drug mimics the effect of neurotransmitter by binding to the same binding site
• Receptor blocker/Direct antagonist


  Drug binds with the receptors but does not open the ion channel, preventing the neurotransmitter from opening the ion channel
• Competitive binding


  Direct agonists and antagonists act directly on the neurotransmitter binding site
• Noncompetitive binding


  Indirect agonists and antagonists act on an alternative binding site and modify the effects of the neurotransmitter on opening of the ion channel
• Agonist


  A drug that facilitates the effects of a particular neurotransmitter on the postsynaptic cell
• Antagonist


  A drug that opposes or inhibits the effects of a particular neurotransmitter on the post-synaptic cell
• Direct agonist


  A drug that binds with and activates a receptor
• Receptor blocker/Direct antagonist


  A drug that binds with the receptor but does not activate it; prevents the natural ligand from binding with the receptor
• Noncompetitive binding


  Binding of a drug to a site on a receptor, does not interfere with the binding site for the principal ligand
• Indirect agonist


  A drug that attaches to a binding site on a receptor and facilitates the action of the receptor; does not interfere with the binding site for the principal ligand
• Indirect antagonist


  A drug that attaches to a binding site on a receptor and interferes with the action of the receptor, does not interfere with the binding site for the principal ligand
• Termination of postsynaptic potential

  1. Molecules of the neurotransmitter are taken back into terminal button through reuptake

  2. Neurotransmitter is destroyed by an enzyme
• Drug interference with reuptake or destruction of neurotransmitter


  1. Drugs attach to transporter molecules responsible for reuptake and inactivate them, blocking reuptake

  2. Drugs bind with the enzyme that normally destroys the neurotransmitter and prevents it from working
• Agonist drugs


  Prolong the presence of the neurotransmitter in the synaptic cleft
• Synaptic transmission


  1. Synthesis of the neurotransmitter

  2. Storage in synaptic vesicles

  3. Release into the synaptic cleft

  4. Interaction with postsynaptic receptors

  5. Opening of ion channels in the postsynaptic membrane

  6. Termination by reuptake or enzymatic deactivation
• Steps that can be interfered with by antagonist drugs

  • Increase the pool of available precursor
  • Block a biosynthetic enzyme
  • Prevent the storage of neurotransmitter in the synaptic vesicles
  • Stimulate or block the release of the neurotransmitter
  • Stimulate or block presynaptic or postsynaptic receptors
  • Retard reuptake
  • Deactivate enzymes that destroy the neurotransmitter postsynaptically or presynaptically
• Neurotransmitters


  • Acetylcholine
  • Gamma-aminobutyric Acid (GABA)
  • Dopamine
  • Glycine
  • Norepinephrine
  • Opioids
  • Serotonin
  • Adenosine
  • Glutamate
  • Nitric oxide
• Acetylcholine (ACh)


  • Primary neurotransmitter secreted by efferent axons of the CNS
  • Responsible for all muscular movement
  • Also found in the ganglia of the ANS and at the target organs of the parasympathetic branch of the ANS
• Acetylcholinergic synapses


  Synapses that release acetylcholine
• Effects of ACh in the brain

  • Generally facilitatory
  • Acetylcholinergic neurons in the dorsolateral pons are responsible for eliciting most of the characteristics of REM sleep
  • Acetylcholinergic neurons in the basal forebrain are involved in activating the cerebral cortex and facilitating learning, especially perceptual learning
  • Acetylcholinergic neurons in the medial septum control the electrical rhythms of the hippocampus and modulate its functions, which include the formation of particular kinds of memories
• ACh receptors

  Ionotropic and metabotropic
• Nicotinic ACh receptor


  Stimulated by nicotine
• Muscarinic ACh receptor


  Stimulated by muscarine
• Muscarinic receptors


  Metabotropic, control ion channels through second messengers, have slower and more prolonged actions than nicotinic receptors
• Monoamines


  • Epinephrine, norepinephrine, dopamine, and serotonin
  • Catecholamines: epinephrine, norepinephrine, dopamine
• Dopamine


  • Produces both excitatory and inhibitory postsynaptic potentials, depending on the postsynaptic receptor
  • Implicated in functions including movement, attention, learning, and the reinforcing effects of drugs
• Dopamine pathways

  Mesolimbic system/pathway: originates in the ventral tegmental area (VTA) in the midbrain, highly involved in pleasure and reward
• Monoamines


  Neurotransmitters produced by several systems of neurons in the brain
• Dopamine


  One of the catecholamines, produces both excitatory and inhibitory postsynaptic potentials depending on the post synaptic receptor
• Dopamine


  • Implicated in several important functions, including movement, attention, learning, and the reinforcing effects of drugs that people tend to abuse
• Major dopamine pathways in the brain

  • Mesolimbic system
  • Mesocortical system
  • Nigrostriatal system
  • Tuberoinfundibular system