Effect of inosine on seizures induced with pentylenetetrazole, bicuculline, or picrotoxin.
The effect in mice of inosine administered subcutaneously on the threshold of seizures induced with pentylenetetrazole (PTZ), bicuculline, and picrotoxin was studied, and brain inosine levels were measured. Following inosine, 1,000 mg/kg, the threshold to PTZ was increased at 10-30 min after injection as determined by a tail vein infusion method. Bicuculline and picrotoxin thresholds were significantly elevated only at 5 min. The time to the first myoclonic jerk after intraperitoneal administration of each of these convulsants was significantly prolonged by the lowest dose of inosine tested (250 mg/kg for PTZ, 100 mg/kg for bicuculline, and 500 mg/kg for picrotoxin). Inosine was given subcutaneously 10 min before the convulsant. The mean control brain inosine concentration was 2.9 microM. After subcutaneous inosine, 1,000, 500, and 250 mg/kg, the highest levels reached were 14.4, 7.9, and 4.3 microM, respectively. It is concluded that micromolar concentrations of inosine in brain are antiepileptic.
D000818:Animals; D001640:Bicuculline / Q000037:antagonists & inhibitors; D004831:Epilepsies, Myoclonic / Q000503:physiopathology*; D007263:Infusions, Parenteral; D007288:Inosine / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010433:Pentylenetetrazole / Q000037:antagonists & inhibitors; D010852:Picrotoxin / Q000037:antagonists & inhibitors; D013997:Time Factors
D001640:Bicuculline; D007288:Inosine; D010433:Pentylenetetrazole; D010852:Picrotoxin