Receptors

[Ref: SH4:p21]

GABAa receptors

Coupled with a chloride ion channel

Activation
--> Opening of Cl- ion channel
--> Hyperpolarisation

 

Activated by

• Benzodiazepines, barbiturates, propofols
• Volatile anaesthetics

 

GABA-mediated inhibition is produced by:

• Increased agonist affinity for GABAa receptor
• Prolongation or augmentation of chloride conductance

Anaesthetic and GABAa receptors

Complete anaesthetic cannot be provided by GABAa-agonist actions of hypnotic drugs
* e.g. benzodiazepines, barbiturates, propofol, etomidate

Opioids and alpha2 agonists inhibits presynaptic calcium ion channel
* Responsible for neurotransmitter release

Thus,

Combination of activation of GABAa and inhibition of presynaptic calcium channel
--> Full anaesthetics

Volatile anaesthetics may provide both

Glycine receptors

• Glycine receptors are closely related to GABAa receptors
• Inhibitory
• Mainly in spinal cord
• Activity is enhanced by volatile anaesthetics

 

5-Hydroxytryptamine (5-HT) receptors

Subtypes

• 5HT3 subtype is ligand-gated
• All other subtypes are metabotropic (i.e. G-protein coupled)

Properties

• Excitatory
• Selectively permeable to cations
• Actions in CNS include anxiolysis, analgesia, and emetic

Glutamate receptors

Glutamate acts on a variety of receptors
* Both metabotropic and ionotropic

Ionotropic (i.e. ligand-gated) glutamate receptors

• AMPA receptors
• NMDA receptors
• Kainate receptors

NB:

AMPA = Alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid

NMDA = N-methyl-D-aspartate

NMDA receptors

• Voltage sensitive
• Glutamate sensitive
• Requires glycine as a obligatory co-agonist
• Blockade by Mg2+ ion
• Also acted on by ketamine, xenon, N2O, methadone