Interactions of anesthetics with their targets: Non-specific, specific or both?

What makes a general anesthetic a general anesthetic? We shall review first what general anesthesia is all about and which drugs are being used as anesthetics. There is neither a unique definition of general anesthesia nor any consensus on how to measure it. Diverse drugs and combinations of drugs generate general anesthetic states of sometimes very different clinical quality. Yet the principal drugs are still considered to belong to the same class of ‘general anesthetics’. Effective concentrations of inhalation anesthetics are in the high micromolar range and above, and even for intravenous anesthetics they do not go below the micromolar range. At these concentrations, many molecular and higher level targets are affected by inhalation anesthetics, fewer probably by intravenous anesthetics. The only physicochemical characteristic shared by anesthetics is the correlation of their anesthetic potencies with hydrophobicity. These correlations depend on the group of general anesthetics considered. In this review, anesthetic potencies for many different targets are plotted against octanol/water partition coefficients as measure of hydrophobicity. Qualitatively, similar correlations result, suggesting several but weak interactions with proteins as being characteristic of anesthetic actions. The polar interactions involved are weak, being roughly equal in magnitude to hydrophobic interactions. Generally, intravenous anesthetics are noticeably more potent than inhalation anesthetics. They differ considerably more between each other in their interactions with various targets than inhalation anesthetics do, making it difficult to come to a decision which of these should be used in future studies as representative ‘prototypical general anesthetics’.