Exception of Meyer-Oveon rule are all except
Meyer-Oveon correlation of anesthetic potency with solubility in olive oil interpreted by the majority of researchers as an indicator that lipids are likely the anesthetic target. This interpretation focused attention on anesthetic effects on the bulk physical propeies of cell membranes, which were known at that time to consist primarily of lipid molecules. Such nonspecific or "lipoid-based" anesthetic theories dominated the field from the 1960s to the 1980s. Moreover, the simple elegance of the relationship between MAC and lipid solubility graphically illustrated Meyer and Oveon's conclusion that "All chemically indifferent substances that are soluble in fat are anesthetics ... their relative potency as anesthetics will depend on their affinity to fat on the one hand and water on the other hand, that is, on the fat/water paition coefficient. This was interpreted as oring lipids as the primary targets of anesthetics and a single nonspecific theory to explain anesthesia. Objections to the outdated lipid hypotheses: 1. Stereoisomers of an anesthetic drug Stereoisomers that represent mirror images of each other are termed enantiomers or optical isomers (for example, the isomers of R-(+)- and S-(-)-etomidate). Physicochemical effects of enantiomers are always identical in an achiral environment (for example in the lipid bilayer). However, in vivo enantiomers of many general anesthetics (e.g. isoflurane, thiopental, etomidate) can differ greatly in their anesthetic potency despite the similar oil/gas paition coefficients. For example, the R-(+) isomer of etomidate is 10 times more potent anesthetic than its S-(-) isomer 2. Non-immobilizers According to the Meyer-Oveon correlation, the anesthetic potency of the drug is directly propoional to its lipid solubility, however, there are many compounds that do not satisfy this rule. These drugs are strikingly similar to potent general anesthetics and are predicted to be potent anesthetics based on their lipid solubility, but they exe only one constituent of the anesthetic action (amnesia) and do not suppress movement (i.e. do not depress spinal cord functions) as all anesthetics do. These drugs are referred to as non-immobilizers. 3. Temperature increases do not have an anaesthetic effect 4. Effect vanishes beyond a ceain chain length According to the Meyer-Oveon correlation, in a homologous series of any general anesthetic (e.g. n-alcohols, or alkanes), increasing the chain length increases the lipid solubility, and thereby should produce a corresponding increase in anesthetic potency. However, beyond a ceain chain length, the anesthetic effect disappears. For the n-alcohols, this cutoff occurs at a carbon chain length of about 13 and for the n-alkanes at a chain length of between 6 and 10, depending on the species. 5. Non-hydrophobic anesthetics. Ref: Miller's anesthesia 8th edition Ref: Morgan & Mikhail's clinical anesthesiology 6e
Non anaesthetics
Non immobilizer
Cut off effect
Hydrophobic site of action
Fundamental concepts