Reduction of motor seizures in rats induced by the ethyl bicyclophosphate trimethylolpropane phosphate (TMPP)

1. Trimethylolpropane phosphate (TMPP) is a potent cage convulsant, reporte d to act through binding to the picrotoxinin and/or benzodiazepine receptor sites of the gamma-aminobutyricA (GABA(A)) ionophore complex. 2. Adult male Fischer-344 rats were pretreated by intraperitoneal (ip) inje ction with either diazepam (DZP) [0.5-5.0 mg/kg], Phenobarbital (PB) [5-20 mg/kg], dizocilpine maleate (MK-801) [0.5-3.0 mg/kg], Tiagabine (TGB) [0.5- 5.0 mg/kg], 6,7-dinitro-quinoxaline-2,3-dione (DNQX), [5-20 mg/kg], or scop olamine [SCP] (0.25-1.0 mg/kg) 30 min prior to ip injection with a convulsi ve dose of TMPP (0.6 mg/kg). 3. Rats were rated for occurrence of convulsive activity for 120 min post-i njection. Time From TMPP injection to observation of subclinical seizures, generalized (tonic-clonic) seizures, and lethality was rated for each pretr eatment group. 4. In general, DZP = PB > TGB in reduction of TMPP subclinical and/or clini cal seizures. MK-801, at dose levels inducing near sedation, was also effec tive in modulation of TMPP-induced seizures. SCP or DNQX were generally ine ffective in reducing or eliminating TMPP-induced seizures.