Correlating in vivo anaesthetic effects with ex vivo receptor density datasupports a GABAergic mechanism of action for propofol, but not for isoflurane

If the in vivo effects of anaesthesia are mediated through a specific recep tor system, then a relationship could exist between the regional changes in bt ain metabolism caused by a particular agent and the underlying regional distribution of the specific receptors affected by that agent. Positron em ission tomography data from volunteers studied while unconscious during pro pofol (n=8) or isoflurane (n=5) anaesthesia were used retrospectively to ex plore for evidence of relationships between regional anaesthetic effects on brain glucose metabolism and known (ex vivo) regional distribution pattern s of human receptor binding sites. The regional metabolic reductions caused by propofol differed significantly from those of isoflurane, Propofol's re ductions negatively correlated most significantly with the regional distrib ution of [H-3]diazepam and [H-3]flunitrazepam (benzodiazepine) binding site densities (r=-0.86, P<0.0005; r=-0.79, P<0.005, respectively) and less str ongly with [H-3]naloxone (opioid) binding density (r=-0.69, P<0.05). Isoflu rane's reductions positively correlated only with muscarinic (acetylcholine ) binding density (r=0.85, P<0.05). These findings are consistent with the hypothesis that some of propofol's in vivo anaesthetic effects may be media ted through a GBBAergic mechanism and suggest some of isoflurane's in vivo effects might involve antagonism of central acetylcholine functioning.