Reduction of motor seizures in rats induced by the ethyl bicyclophosphate trimethylolpropane phosphate (TMPP).
1. Trimethylolpropane phosphate (TMPP) is a potent cage convulsant, reported 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 (i.p.) injection 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 scopolamine [SCP] (0.25-1.0 mg/kg) 30 min prior to i.p. injection with a convulsive dose of TMPP (0.6 mg/kg). 3. Rats were rated for occurrence of convulsive activity for 120 min post-injection. Time from TMPP injection to observation of subclinical seizures, generalized (tonic-clonic) seizures, and lethality was rated for each pretreatment group. 4. In general, DZP = PB > TGB in reduction of TMPP subclinical and/or clinical seizures. MK-801, at dose levels inducing near sedation, was also effective in modulation of TMPP-induced seizures. SCP or DNQX were generally ineffective in reducing or eliminating TMPP-induced seizures.
Rossi
J
J
Neurobehavioral Effects Laboratory, Naval Health Research Center Detachment-Toxicology, Wright-Patterson Air Force Base, OH 45433, USA.
Ritchie
G D
GD
McInturf
S
S
Nordholm
A F
AF
D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000009:adverse effects*; D003292:Convulsants / Q000009:adverse effects*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D018079:Receptors, GABA / Q000502:physiology; D012640:Seizures / Q000139:chemically induced* / Q000188:drug therapy* / Q000503:physiopathology
D000927:Anticonvulsants; D019086:Bridged Bicyclo Compounds, Heterocyclic; D003292:Convulsants; D018079:Receptors, GABA; C065518:4-ethyl-1-phospha-2,6,7 trioxabicyclo(2.2.2)octane-1-oxide