The exact site of mechanisms of action of inhalation anesthetics is not certain but possible sites are macroscopic (CNS-brain), microscopic (axons and synapses) and molecular (pre- and postsynaptic membranes).
Hence, the possible mechanisms of action of inhalation anesthetics is varied:
a) Multiple receptor sites
b) Motor inhibition at spinal cord level
c) Many neurotransmitters are involved
• Neuronal and muscle nicotinic acetylcholine receptor.
• Serotonin-5HT3 receptor channels.
• Inhibitory GABA type A receptor channel.
• Glycine receptor channel.
d) The Meyer-Overton rule stating lipid solubility in cellular hydrophobic regions.
e) Direct binding to cell membrane proteins and lipids.
Also, as per the mechanisms of action of inhalation anesthetics , the potency of an anaesthetic is measured by determining the response of an animal to a well-defined stimulus. Firstly, the righting reflex, the ability of an animal to right itself after it is turned over; secondly, the ability of an animal to respond with a purposeful movement when subjected to a painful stimulus like a tail-clamp. Mice and tadpoles are used for this experiment.
Ferguson’s rule states a correlation between anaesthetic potency and vapour pressure. General anaesthesia can be reversed by high pressure; this is known as pressure reversal of anaesthesia.To summarize the mechanisms of action of inhalation anesthetics :
1. Mechanisms of action of inhalation anesthetics general is still not fully resolved; a specific antagonist is lacking.
2. General anaesthetics block synaptic transmission at concentrations much less than those required to block axonal conductance.
3. There are two theories of mechanisms of action of inhalation anesthetics general—unitary theory, which means that all general an- aesthetics act by a common mechanism; and the degenerate theory, which states that different anaesthetic groups have different mechanisms of action.
4. General anaesthesia can be produced by a simple inert gas (xenon) as well as complex molecules like althesin (steroid), hence there is no specific receptor.
5. Lipid solubility and potency of general anaesthetics is expressed by the Meyer-Overton rule.
6. For mechanisms of action of inhalation anesthetics and at the molecular level, there are three possible sites of action:
a) The lipid layer
b) The cellular neurotransmitter proteins
c) The lipid-protein interface. Lipid layer expansion may obstruct ion channels.
7. There may be inhibition of both acetylcholine receptor channels (nicotinic receptors) and the GABA receptor – channels. GABA enhances inward movement of chloride ions. In mechanisms of action of inhalation anesthetics the protein binding occurs at various sites, namely, soluble proteins, membrane proteins, ligandgated ion channels and G-proteins.