Neurotransmitters

Describe the major neurotransmitters and their physiological role, with particular reference to GABA, excitatory and inhibitory amino acids, acetylcholine, noradrenaline, dopamine and serotonin and NMDA receptor

GABA

Gamma aminobutyric acid is the major inhibitory CNS neurotransmitter. GABA receptors have three subtypes:

• GABA_A
  Inotropic receptor important for the action of many drugs.
  • Pentameric structure
    • 2 α
      Bind GABA.
    • 2 β
    • 1 γ
  • Affected by many different drugs:
    • Benzodiazepines
      Positive allosteric modulation at at the α/γ interface.
    • General anaesthetic agents
      Including propofol, barbiturates, halogenated volatiles, and etomidate.
      • Act at the β subunit
        Cause a conformational change which increases Cl^- opening time, hyperpolarising the cell.
• GABA_B
  Metabotropic receptor.
• GABA_C
  Inotropic receptor located only in the retina.

NMDA

N-methyl D-aspartate receptor is an inotropic receptor that is:

• Agonised by glutamate
  • Glycine is co-agonist
• Voltage dependent
  • Central pore usually blocked by an Mg²⁺ ion
  • Becomes unblocked when partially depolarised
• Important in the action of drugs which do not act at the GABA_A receptor
  Antagonised by:
  • Ketamine
  • Xenon
  • N₂O

References

1. Petkov V. Essential Pharmacology For The ANZCA Primary Examination. Vesselin Petkov. 2012.