Double-blind crossover controlled study on antiepilepsirine.

Antiepilepsirine (AES) is one of the derivatives of a Chinese folk prescription. It is a new antiepileptic drug (AED) synthesized in cooperation by Chinese medical and pharmaceutical workers. Pharmacological experiments on animal models prove that its antiepileptic action is marked, but there has been little evaluation of its clinical effects. We used the double-blind placebo-controlled crossover study which is generally acceptable as a proper method for new drug study. This study covered 58 epileptic children treated with classical AEDs and observed 6.5 months. Every patient took AES and placebo for 3 months each by random crossover on the basis of add-on therapy. The blood levels of AES and other antiepileptic drugs were determined regularly. The results show that there are no significant differences in clinical effects between AES and placebo in pediatric epilepsies as a whole, but AES is effective in tonic-clonic seizures (P less than 0.05), the most common type of seizure in the series. There are no significant differences in AED blood levels between the AES effective and ineffective groups. AES has no effect on the blood levels of other AEDs. AES is very safe, children given large doses (10 mg/kg/day) demonstrate no serious side-effects. It is suggested that there is potential improvement in patient psychological and cognitive status. This article also discusses the evaluation of new drugs for clinical effects, subject sampling, the criteria for efficacy evaluation and relationship between animal information and human outcome. The AES chemical structure is different from other well-known AEDs, this is a unique advantage.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of lipid peroxidation on GABA uptake and release in iron-induced seizures.

Intraventricular injection of iron causes seizures and lipid peroxidation in brain tissue. To determine the effects of iron-induced lipid peroxidation on GABA uptake and release, synaptosomal fraction was prepared from 30-day-old iron-treated and control Wistar rats. Our data demonstrated that GABA release was more severely damaged than GABA uptake by lipid peroxidation. This imbalance between release and uptake may reduce GABA inhibition, which could contribute to the neurochemical pathogenesis of iron-induced seizures.

Kindling phenomenon of hyperthermic seizures in the epilepsy-prone versus the epilepsy-resistant rat.

A kindling-like effect was produced by exposing 30-day-old rats to repeated hyperthermia-induced seizures. Naive audiogenic seizure (AGS)-susceptible rats (P77PMC) were easier to be kindled than AGS-resistant rats (Wistar). This hyperthermic kindling model may be used to study the outcome and mechanisms of human febrile seizures. The mechanisms underlying hyperthermic kindling remain to be investigated.

Seizures induced by intraventricular microinjection of ionized cobalt in the rat--a new experimental model of epilepsy.

A new animal model for epilepsy was successfully produced by microinjection of cobaltous chloride into the lateral cerebral ventricle of the rat. The median convulsive dose (CD50) and the median lethal dose (LD50) of CoCl2 was 0.45 microM/10 microliters (0.27-0.77 microM/10 microliters) and 1.07 microM/10 microliters (0.73-1.57 microM/10 microliters), respectively. The behavioral changes, electrocorticogram (ECoG), and the action of 5 classical anticonvulsants were studied using this new model. Seizures induced by cobaltous chloride are clinically similar to those produced by systemic administration of kainic acid and amygdala kindling. These are characterized by staring spells, wet dog shakes, mild convulsive movements, and stereotyped convulsions. ECoG findings demonstrated a unique epileptic burst during the wet dog shakes. Generalized epileptiform discharges were seen during typical seizures. The burst of spikes first occurred in the opposite temporal and frontal regions; and then became generalized. Among the 5 anticonvulsants studied, phenobarbital (30 mg/kg) and nitrazepam (3 mg/kg) completely antagonized the seizures; carbamazepine showed a moderate effect; and phenytoin as well as sodium valproate showed little effect. It is postulated that the seizures induced by cobaltous chloride may originate in the limbic system; and that cobalt ions are responsible for the seizure-inducing action. The mechanism remains to be investigated.

Long-term effects of febrile convulsion on seizure susceptibility in P77PMC rat--resistant to acoustic stimuli but susceptible to kainate-induced seizures.

A new audiogenic seizure (AGS)-susceptible strain of rats (P77PMC) was evaluated as a possible model of human febrile seizures. The long-term effects of experimental febrile seizures were observed. All 30-day-old rat pups exhibited clonic seizures during exposure to an ambient temperature of 45 +/- 0.5 degree C. The mean latency from the beginning of the hyperthermic stimulus to the onset of convulsion was 16.9 +/- 2.2 min. The rats survived this hyperthermic seizure, developed a resistance to acoustic stimulations, but were more susceptible at the age of 50 to 60 days to kainate-induced limbic seizures than controls. The results of this study imply that febrile seizures of developing P77PMC rats can change later seizure susceptibility, and there may be some correlation between febrile convulsion and temporal lobe epilepsy.