[The effect of neuroleptics and neuroleptic/analgesic combinations on the sensitivity to seizures in mice].

Combinations of neuroleptic and morphine-like analgesic drugs are used alone for minor surgery or as anesthetic premedication. While morphine-like analgesics given in the therapeutic dose range show anticonvulsant properties, there is evidence indicating that neuroleptics are rather proconvulsant. This study was performed to investigate the influence of the most widely used combinations pethidine/promethazine and fentanyl/droperidol on seizure susceptibility.

METHODS

Thresholds for convulsions induced by electroshock and pentetrazole infusion were used as models for seizure susceptibility. The drugs tested were injected s.c. 20-30 min before determination of the seizure threshold.

RESULTS

Pethidine/promethazine and fentanyl/droperidol reduced the susceptibility to seizures induced by electroshock. Promethazine and droperidol alone elevated the threshold only at the highest doses used (2 mg/kg and 2.5 mg/kg respectively). Promethazine, whether given alone or in combination with pethidine, showed no effect on the threshold for pentetrazole-induced convulsions. Droperidol alone lowered the threshold for pentetrazole-induced clonic convulsions only at the lowest dose used (0.625 mg/kg), but lowered that for tonic convulsions at all doses studied (0.625, 1.25 and 2.5 mg/kg). The combination of fentanyl and droperidol lowered the threshold for both clonic and tonic convulsions at the two lower doses (12.5 micrograms/kg fentanyl + 0.625 mg/kg droperidol and 25 micrograms/kg fentanyl + 1.25 mg/kg droperidol). Only the highest dose studied (50 micrograms/kg fentanyl + 2.5 mg/kg droperidol) showed no significant effect.

CONCLUSIONS

Pethidine and fentanyl show anticonvulsant properties in mice, but it is evident from our results that there is some interaction between their combinations with neuroleptics and seizure susceptibility. This is more pronounced with the combination fentanyl/droperidol in the model of pentetrazole-induced convulsions.(ABSTRACT TRUNCATED AT 250 WORDS)