Species variation and the mechanism of pressure-anaesthetic interactions.

The mechanism of general anaesthesia has proved difficult to elucidate (see ref. 1 for a review), although the relative potencies of anaesthetic agents have been used to establish that the site at which anaesthetics act is hydrophobic in nature. One further clue to their mode of action is that the effects of anaesthetics on vertebrates can be eliminated by pressures of approximately 100 atm (refs 3, 4). However, the effects of anaesthetics are not always reversed in model systems, where there is evidence that the pattern of pressure reversal varies significantly. We now find that pressure fails to reverse the effects of anaesthetics on the freshwater shrimp (Gammarus pulex), although the sensitivity of these crustaceans to anaesthetics is comparable with that of higher animals. This is hard to reconcile with traditional bio-physical mechanisms and indicates that anaesthetics may act at a specific protein site rather than having a general effect on cell membranes. The pharmacology of pressure in mammals seems to be more similar to that of strychnine than of any other central stimulant. As glycine, whose action is blocked by strychnine, is absent as a neurotransmitter in the arthropod central nervous system, we believe that this substance may be involved in determining pressure-anaesthetic interactions in vertebrates.