Neurotransmitter

Aka: Neurotransmitter, Neurotransmitter Physiology

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II. Definitions

  1. Neurotransmitter
    1. Endogenous signaling molecules affecting Neuron behavior by acting at nerve Synapse, Muscle Cells and glands
    2. Neurotransmitters are synthesized and released by Neurons

III. Physiology: Neurotransmitters in General

  1. More than 500 Neurotransmitters have been identified in humans
  2. Chemical Structures
    1. Amino Acids (e.g. Glutamate, Aspartate, Gamma-Aminobutyric Acid or GABA, Glycine)
    2. Monoamines (e.g. Dopamine, Norepinephrine, Epinephrine, Histamine, Serotonin)
    3. Peptides (Oxytocin, Somatostatin, substance P)
    4. Purines (Adenosine Triphosphate or ATP, Adenosine)
    5. Miscellaneous (Acetylcholine or ACh)
  3. Function
    1. Excitatory Neurotransmitters
      1. Acetylcholine
      2. Norepinephrine
      3. Glutamate
        1. Excitatory Amino Acid (EAA) facilitate CNS Neuron depolarization
          1. Increases cation conductance and phostatidyl Inositol turnover
        2. Important Neurotransmitter in memory and learning
        3. Implicated in pathogenesis of Alzheimer's Disease, huntington disease, Seizure Disorder and ALS
    2. Inhibitory Neurotransmitters
      1. Dopamine
        1. Produced in Substantia Nigra and released into Basal Ganglia
      2. Gamma-Aminobutyric Acid (GABA)
        1. Broad distribution (see below)
      3. Glycine
        1. Produced in spinal cord
      4. Serotonin
        1. Produced in median raphe and Hypothalamus
    3. Neurotransmitters with Sedative and Analgesic properties (Opioid-like)
      1. Endorphins
      2. Enkephalins
  4. Neuroendocrine Brain Regions (Pigmented Regions)
    1. Locus Ceruleus
      1. NorepinephrineSecreting nucleus in pons
      2. Important in wakefulness and attention
    2. Substantia Nigra
      1. DopamineSecreting region in Midbrain
      2. Substantia Nigra degeneration results in Dopamine deficiency and Parkinsonism

IV. Physiology: GABA and NMDA

  1. N-methyl-D-Aspartate (NMDA) receptor
    1. Glutamate binds NMDA receptors and results in excitation
    2. NMDA receptors are up regulated in chronic Alcohol Abuse
    3. NMDA Antagoists include Ketamine
  2. Gamma-Aminobutyric Acid (GABA) receptor
    1. GABA Agonists bind GABA Receptors, resulting in inhibition
    2. GABA Receptors are down regulated in chronic Alcohol Abuse

V. Physiology: Neurotransmitter at Synapse

  1. Medications affecting Precursor Uptake
    1. L-Phenylalanine
    2. L-Tyrosine
    3. L-Dopa
    4. Dopamine (DA)
    5. Norepinephrine (NE)
    6. Epinephrine (E)
    7. L-Tryptophan
    8. 5-Hydroxytryptophan,
    9. 5-Hydroxytryptamine (5-HT) = Serotonin
    10. Choline/lecithin + AcetylCoA => Acetylcholine (Ach)
  2. Medications affecting Synthetic Enzymes
    1. Metyrosine (Demser) blocks Tyrosine hydroxylase
      1. Decrease DA, NE, E, 5HT
    2. Methyldopa (Aldomet) blocks decarboxylation
      1. Decrease DA, NE, E, 5HT
  3. Medications affecting Transfer into Vesicle
    1. No clinically available drugs
  4. Medications affecting Vesicle storage
    1. Reserpine (Serpasil) depletes storage
    2. Decreases DA, NE, E, 5HT
  5. Medications affecting Vesicle mobilization
    1. Affects Nerve Impulse Conduction Vesicle release
    2. Electroconvulsive Therapy decreases DA, NE, E, 5HT
  6. Medications affecting Post-synaptic receptors
    1. Reversible receptor blockade by Neuroleptics (Haldol)
  7. Medications affecting Neurotransmitter reuptake
    1. Reuptake inhibition by all Antidepressants (Prozac)
  8. Medications affecting Neurotransmitter breakdown
    1. No drugs available
  9. Medications affecting Neurotransmitter dilution
    1. No drugs available
  10. Medications affecting Neurotransmitter breakdown
    1. Monamine oxidase inhibitor (MOAi) (Parnate, Nardil)
    2. Tacrine Inhibits Acetylcholinesterase
      1. Increases Acetylcholine

VI. Physiology: Neurotransmitter Theory applied to Psychiatric Medication

  1. Neuroleptics
    1. Deplete Neurotransmitter Stores
      1. Rauwolfia alkaloids (e.g. Reserpine)
      2. Phenothiazine: Chlorpromazine (Thorazine)
      3. Thioxanthenes: Thiothixene (Navane)
      4. Butyrophenones: Haloperidol (Haldol)
    2. Receptor blockade
      1. Lithium Carbonate
      2. Interferes with Neurotransmitter storage Na-K Pump
  2. Stimulants
    1. Mimic Neurotransmitter at storage or Receptor sites
      1. Amphetamines: Methamphetamine (Methedrine)
      2. Benzyl-piperidines: Methylphenidate (Ritalin)
  3. Antidepressants: MAO Inhibitors
    1. Monoamine Oxidase (MAO) is a naturally in-vivo enzyme that metabolizes Serotonin and Norepinephrine
      1. Inactivation or inhibition of MAO results in increased levels of Serotonin and Norepinephrine
    2. Tranylcypromine (Parnate)
      1. Inactivate MAO
    3. Polycyclic: Imipramine HCl (Tofranil)
      1. Inhibit MAO reuptake
  4. Antidepressants: SSRI and SNRI
    1. Decreased Serotonin and norephinephrine are associated with Major Depression
    2. Reuptake inhibitors increase these Neurotransmitters in the Synapse by blocking reuptake
      1. Selective Serotonin Reuptake Inhibitors (SSRI)
      2. Serotonin Norepinephrine Reuptake Inhibitors (SNRI)

VII. Resources

  1. Neurotransmitters (Wikipedia)
    1. https://en.wikipedia.org/wiki/Neurotransmitter

VIII. References

  1. Goldberg (2014) Clinical Physiology, MedMaster, p. 88

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