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Abstract:
Almost a century ago, Meyer and Overton discovered a linear relationship between the potency of anaesthetic agents to induce general
anaesthesia and their ability to accumulate in olive oil. Similar correlations between anaesthetic potency and lipid solubility were later reported from
investigations on various experimental model systems. However, exceptions to the Meyer-Overton correlation exist in all these systems, indicating that lipid
solubility is an important, but not the sole determinant of anaesthetic action. In the mammalian central nervous system, most general anaesthetics act at
multiple molecular sites. It seems likely that not all of these effects are involved in anaesthesia. GABAA- and NMDA-receptor/ion channels have already
been identified as relevant targets. However, further mechanisms, such as a blockade of Na+ channels and an activation of K+ channels, also come into play.
A comparison of different anaesthetics seems to show that each compound has its own spectrum of molecular actions and thus shows specific, fingerprint-like
effects on different levels of neuronal activity. This may explain why there is no known compound that specifically antagonises general anaesthesia. General
anaesthesia is a multidimensional phenomenon. Unconsciousness, amnesia, analgesia, loss of sensory processing and the depression of spinal motor reflexes
are important components. It was not realised until very recently that different molecular mechanisms might underlie these different components. These
findings challenge traditional views, such as the assumption that one anaesthetic can be freely replaced by another.
