Interactions between opioid drugs and propofol in laboratory models of seizures.

Propofol (i.v. and i.p.) exhibited anticonvulsant activity in three models of seizure in the mouse, induced by bicuculline, kainic acid and N-methyl-DL-aspartic acid (NMDLA). Morphine, pethidine and fentanyl, which showed a biphasic dose-response relationship with respect to seizure modulation, abolished the anticonvulsant activity of propofol to exhibit their own intrinsic activity in proconvulsant doses. This occurred with very low doses of fentanyl and pethidine (15 micrograms kg-1 and 0.5 mg kg-1, respectively) in the NMDLA model. Thus it appears that propofol has anticonvulsant activity only when a convulsion is elicited directly; it does not prevent the actions of compounds that lower seizure threshold to convulsant stimuli. The anticonvulsant doses of morphine and fentanyl did not summate with the anticonvulsant activity of propofol. However, there was some evidence of summation of anticonvulsant activity between pethidine and propofol in the NMDLA model.