3. Old stuff
          3.1. Old pharm stuff (pre 2009)
              3.1.3. Pharmacology
                  3.1.3.2. Inhalational anaesthetic agents
                      3.1.3.2.2. Pharmacodynamics of inhalational anaesthetics
 3.1.3.2.2.2. Mechanism of immobility by inhalational anaesthetics 

Mechanism of immobility

[Ref: SH4:p35-38]

  • Inhalational anaesthetic agents produce immobility
    * By acting on the spinal cord
    * NOT by acting on higher centres

Mechanisms

  • Depression of excitation
    * e.g. AMPA and NMDA receptor-mediated currents
  • Enhancement of inhibition
    * e.g. GABAa and glycine receptor-mediated currents
  • Actions of Na+ channel (but not K+ channel)

However,

  • Cholinergic receptors do not play a significant role
  • Opioid receptors are not involved

NB:

From [SH4:p36]

"Overall, no inhaled anaesthetic action on a single group of receptors can explain immobility, and immobility as a result of concurrent actions on many receptors is unlikely"

--> ???

Inhibitory receptors

  • Glycine receptors are major mediators of inhibitory neurotransmission in the spinal cord
    --> Mediates part of the immobility produced by inhalational anaesthetics
  • GABAa receptors mediate immobility produced by IV anaesthetics

GABA and inhalational agent

  • GABAa receptors probably do not mediate immobility produced by inhaled AA [SH4:p36]
  • But at the same time, maximal enhancement of GABAa receptors also occurs at the partial pressure of AA used in clinical practice. [SH4:p38]

Excitatory receptors

  • Glutamate is the principle excitatory neurotransmitter in CNS
  • Glutamate receptors include G-protein coupled receptors and ligand-gated receptors
  • Ligand-gated glutamate receptors include:
    * NMDA receptors
    * AMPA receptors
    * kainate receptors
  • NMDA receptors are important mediators of immobility produced by inhaled AA
  • AMPA mediates the initial (fast) component of excitatory postsynaptic transmission
    --> Likely to be also involved in immobility produced by inhaled AA
  • Role of kainate receptors on MAC is unclear

NB:

[SH4:p37]

??? Inhaled AA acts on NMDA and AMPA receptors in the spinal cord

??? Inahled AA does not act on the same receptors in the brain

Sodium channel

  • Inhaled AA does not inhibit voltage-dependent Na+ channels
  • Inhaled AA inhibits presynaptic Na+ channel and/or voltage-gated calcium ion channel
    --> Inhibition of presynaptic release of neurotransmitter (especially glutamate)
  • Thus, IV lidocaine decreases MAC (via its antagonism action on Na+ channels)