CL 218-872 pretreatment and intervention block kainate-induced convulsions and neuropathology.
Two experiments were conducted to test the antiepileptic properties of CL 218-872, a triazolopyridizine reported to have anxiolytic and anticonvulsant effects without accompanying sedative and ataxic effects. In Experiment 1 pretreatment with CL 218-872, a recently synthesized and potent triazolopyridizine, reduced kainic acid-induced convulsions and subsequent neuropathology in rats given ip doses of 25 mg/kg or greater. CL 218-872 at doses of 50 mg/kg or greater was more effective than a high dose of diazepam (20 mg/kg) in blocking status epilepticus-like convulsions and the associated widespread neuropathological sequelae. Moreover, diazepam pretreatment was associated with a higher mortality rate than CL 218-872. In Experiment 2 the efficacy of intervention with 20 mg/kg diazepam was compared with that of 50 mg/kg CL 218-872 in suppressing ongoing convulsions and reducing subsequent brain damage following a convulsant dose of kainic acid. Although CL 218-872 and diazepam were equally effective behaviorally (i.e., in suppressing kainic acid-induced convulsions), CL 218-872 was superior in its ability to reduce subsequent neuropathology, especially in the hippocampus and neocortex. Because kainic acid has been suggested as a model for human status epilepticus, CL 218-872 may be a potentially therapeutic treatment for this disorder.
Bates
J F
JF
Physiological Psychology Laboratory, Clark Science Center, Smith College.
Peake
L
L
Swearengen
E S
ES
Hall
T W
TW
Standish
L J
LJ
D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects / Q000473:pathology*; D003975:Diazepam / Q000494:pharmacology; D007608:Kainic Acid / Q000633:toxicity*; D008297:Male; D009928:Organ Specificity; D011724:Pyridazines / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains; D012640:Seizures / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*
D000927:Anticonvulsants; D011724:Pyridazines; C021604:CL 218872; D003975:Diazepam; D007608:Kainic Acid