Pressure reversal of alphaxalone/alphadolone and methohexitone in tadpoles: evidence for different molecular sites for general anaesthesia.

Tadpoles were used to study quantitative interactions between high pressure and two intravenous anaesthetics, alphaxalone/alphadolone and methohexitone. The potencies of the two agents were decreased by high pressure but to different extents. The maximum effect was seen in the pressure range 70-130 atmospheres absolute (ATA). The increases in the normobaric anaesthetizing concentration (ED50) required at 100 ATA were alphaxalone/alphadolone:405 +/- 5 (s.d.)%; methohexitone:658 +/- 80 (s.d.)%. For both alphaxalone/alphadalone and methohexitone, the curves obtained when the increase in ED50 was plotted against increasing pressure showed plateaux at pressures above 70 ATA. These data support the concept of the two intravenous drugs causing general anaesthesia by the occupation of separate molecular 'sites' with different but finite capacities.