The activity of opioid analgesics in seizure models utilizing N-methyl-DL-aspartic acid, kainic acid, bicuculline and pentylenetetrazole.
Morphine, fentanyl and pethidine exhibited a biphasic dose response relationship with respect to their effects on seizure thresholds to bicuculline, pentylenetetrazole, N-methyl-DL-aspartate (NMDLA) and kainic acid in mice. The usual pattern was for low doses to be anticonvulsant and higher doses to be proconvulsant. However this pattern was reversed for fentanyl and pethidine when NMDLA was used to induce seizures. The low dose effects of all three opioid drugs was sensitive to 1 mg kg-1 naloxone in all seizure models. The responses to high doses of pethidine were unaffected or enhanced by this dose of naloxone. Naloxone reversed the effects of the higher doses of morphine and fentanyl in all models except bicuculline induced seizures.
Lauretti
G R
GR
Department of Anaesthesia, University of Manchester, U.K.
Ahmad
I
I
Pleuvry
B J
BJ
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D003292:Convulsants / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D051379:Mice; D016202:N-Methylaspartate / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D010433:Pentylenetetrazole / Q000494:pharmacology; D012640:Seizures / Q000139:chemically induced* / Q000503:physiopathology*
D000701:Analgesics, Opioid; D000927:Anticonvulsants; D003292:Convulsants; D009270:Naloxone; D016202:N-Methylaspartate; D007608:Kainic Acid; D010433:Pentylenetetrazole; D001640:Bicuculline