The anticonvulsant action of nafimidone on kindled amygdaloid seizures in rats.
The anticonvulsant effectiveness of nafimidone (1-[2-naphthoylmethyl]imidazole hydrochloride) was evaluated in the kindled amygdaloid seizure model in rats. Nafimidone (3.1-120 mg/kg i.p.) was evaluated at 30 min in previously kindled rats using both threshold (20 microA increments) and supranthreshold (400 microA) paradigms. Nafimidone (25-50 mg/kg) significantly reduced supranthreshold elicited afterdischarge length and seizure severity only at doses with some prestimulation toxicity. The maximum anticonvulsant effectiveness for the 25 mg/kg i.p. dose of nafimidone was seen between 15 and 30 min utilizing a suprathreshold kindling paradigm. Nafimidone did not significantly elevate seizure thresholds at the doses tested; however, nafimidone (3.1-50 mg/kg) reduced the severity and afterdischarge duration of threshold elicited seizures in a non-dose response manner. Drug-induced electroencephalographic spikes were seen in both cortex and amygdala in most kindled rats receiving 100-120 mg/kg i.p. within 30 min of dosing before electrical stimulation. The frequency of spike and wave complexes increased in most of these animals leading to drug-induced spontaneous seizures and death in approximately 25% before electrical stimulation. This study has demonstrated that although nafimidone can modify both threshold and suprathreshold elicited kindled amygdaloid seizures, it lacks significant specificity in this model of epilepsy.
Albertson
T E
TE
Department of Internal Medicine, University of California, Davis 95616.
Walby
W F
WF
D000679:Amygdala / Q000503:physiopathology; D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D007093:Imidazoles / Q000627:therapeutic use*; D007696:Kindling, Neurologic / Q000187:drug effects*; D008297:Male; D009278:Naphazoline / Q000031:analogs & derivatives / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains; D012640:Seizures / Q000188:drug therapy* / Q000503:physiopathology; D013997:Time Factors
D000927:Anticonvulsants; D007093:Imidazoles; D009278:Naphazoline; C038671:nafimidone