Opiate-like analgesic activity in general anaesthetics.

1 The interaction of naloxone with various anaesthetics was studied both in vivo and in vitro.2 Naloxone (10 mg/kg) did not significantly alter the anaesthetic duration of halothane, diethylether, ketamine, pentobarbitone or Althesin.3 Naloxone (10 mg/kg) reduced the analgesic activity of nitrous oxide, ketamine and morphine in the rat tail-flick test. With the exception of pentobarbitone and Althesin, the other anaesthetic agents also induced analgesia but were not antagonized by naloxone.4 Specific [(3)H]-dihydromorphine binding was displaced by the opiates naloxone (IC(50) = 7.6 nm), methionine-enkephalin (Met-enkephalin, IC(50) = 40 nm) and morphine (IC(50) = 54 nm). Similarly, displacement was observed with xylazine (IC(50) = 9 mum), ketamine (IC(50) = 130 mum) and Althesin (IC(50) = 150 mum); other anaesthetics agents tested were inactive in mm concentrations.5 Ketamine (IC(50) = 200 mum) and xylazine (IC(50) = 9.5 mum) were also capable of displacing specific [(3)H]-D-Ala(2)-enkephalin (D-Leu) binding, as were morphine (IC(50) = 95 nm) and Met-enkephalin (IC(50) = 40 nm).6 On the stimulated guinea-pig ileum, Met-enkephalin and morphine inhibited the contractions, the IC(50) values were 30 nm and 50 nm respectively. The anaesthetics ketamine (IC(50) = 10 mum) and Althesin (IC(50) = 8 mum) were active. Xylazine (IC(50) = 12 nm) exhibited considerable potency in inhibiting the contractions on this preparation. Naloxone 0.5 mum produced a 1000 fold shift in the opiate dose-response curve but the anaesthetic responses showed only slight sensitivity to antagonism by naloxone.7 The activity of Althesin was found to be due to the vehicle in which this anaesthetic is solubilised.8 Whilst several anaesthetic agents showed analgesic activity, specific dihydromorphine binding displacement or guinea pig ileum inhibiting activity, these effects showed variable sensitivity to naloxone.