Effect of morphine and morphine-like analgesics on susceptibility to seizures in mice

In mice, the influence of small (analgesic range) doses of morphine, fentanyl, meperidine and pentazocine on the thresholds for seizures induced by electroshock and pentetrazole was studied. The antinociceptive ED50 was determined against writhing induced by acetic acid or morphine (0.43 mg/kg, s.c.), fentanyl (0.018 mg/kg, s.c.), meperidine (2.6 mg/kg, s.c.), and pentazocine (2.0 mg/kg, s.c.). The electroconvulsive threshold was significantly elevated at doses slightly greater than (fentanyl and meperidine) or about twice the antinociceptive ED50 (morphine and pentazocine). Naloxone antagonized this effect in the case of morphine and fentanyl, but not in the case of meperidine and pentazocine. The threshold for clonic convulsions induced by intravenous infusion of pentetrazole was not influenced by morphine, fentanyl and meperidine, in the dose range studied, but was slightly increased by the smaller doses (2 and 4 mg/kg) of pentazocine. The tonic phase of pentetrazole-induced convulsions was suppressed by the larger doses of fentanyl, meperidine and pentazocine, though smaller doses of pentazocine significantly reduced the threshold for the extensor phase.