CENTRAL NEUROTRANSMITTERS

• Synapses


  Drug-modifiable control points within neuronal networks
• Neurotransmitters


  • Sites at which they may operate
  • Degree of specificity with which such sites may be affected
• γ-Aminobutyric acid (GABA)


  • Chief inhibitory neurotransmitter in the mammalian central nervous system
  • Plays an important role in regulating neuronal excitability throughout the nervous system
  • In humans, directly responsible for the regulation of muscle tone
  • In insect species, acts only on excitatory nerve receptors
  • Technically an amino acid, but rarely referred to as such
• In spastic diplegia in humans, GABA absorption by some nerves becomes damaged, which leads to hypertonia of the muscles signaled by those nerves
• GABA


  • Molecular formula: C4H9NO2
  • Molar mass = 103.12 g/mol
  • Melting point 203.7 °C, 477 K, 399 °F
• GABA function


  1. Binding to specific transmembrane receptors

  2. Opening of ion channels to allow flow of chloride ions or potassium ions

  3. Negative change in transmembrane potential, usually causing hyperpolarization
• GABA receptor types


  • GABAA and GABAC ionotropic receptors
  • GABAB metabotropic receptors
• Neurons that produce GABA as their output are called GABAergic neurons, and have chiefly inhibitory action at receptors in the adult vertebrate
• Whether GABA is excitatory or inhibitory depends on the direction (into or out of the cell) and magnitude of the ionic currents controlled by the GABAA receptor
• GABA's role changes from excitatory to inhibitory as the brain develops into adulthood
• Acetylcholine (ACh)


  • Identified as the transmitter at neuromuscular and parasympathetic neuro effector junctions, and at the major synapse of autonomic ganglia
  • Potential central neurotransmitter
• Catecholamines


  • Brain contains separate neuronal systems that utilize three different catecholamines—dopamine, norepinephrine, and epinephrine
  • Each system is anatomically distinct and serves separate, but similar, functional roles within its field of innervations
• Histamine


  • May be a central neurotransmitter
  • Most of these neurons are located in the ventral posterior hypothalamus
  • Give rise to long ascending and descending tracts to the entire CNS
• Histamine receptor types


  • H1 receptors
  • H2 receptors
  • H3 receptors
  • H4 receptors
• H4 receptors appear to couple to Gi/o and Gq, and are postulated to play a role in inflammation and chemotaxis