Effects of phenobarbital, carbamazepine and a combination of both on corazol-induced changes in the bioelectric activity of rat brains.

Combined forms of epileptic seizures are known to require combinations of antiepileptic drugs for their management. This study investigated the effects of such a combination consisting of phenobarbital and carbamazepine (mixed in the 1:4 ratio) as well as the effects of each component used separately on the Corazol-induced bioelectrical brain discharges. The effects were studied in a group of rats that received only a single dose of the drugs, as well as in a group that underwent 14-day anticonvulsant treatments. The bioelectric activity of the brain was recorded using an EEG method. In a single dosage, the combination of phenobarbital and carbamazepine was found to be more effective than its components. The decrease of Corazol-induced discharges was more pronounced in a single administration of the combination than when it was applied repeatedly. Development of a cumulative effect was observed in respect to carbamazepine action on the Corazol-induced discharges.

Changes in the behavioral reactions of experimental animals after repeated treatment and withdrawal of a combination of phenobarbital and carbamazepine.

The present study investigates changes in behavioral reactions, muscle tonus and staticokinetic reflexes of white rats after repeated applications and subsequent discontinuation of a phenobarbital-carbamazepine combination. These changes were compared to those induced by the two preparations when given alone. The study found a reduction in the orientation capacity of animals treated with single applications and repeated dosages (continuing up to four days) of the anticonvulsants phenobarbital and carbamazepine. Withdrawal of the pharmaceuticals is followed by significant changes in the motor activity and orientation capacity. This is especially apparent on the third day after the pharmaceutical combination was applied. Changes in the other parameters are insignificant, ambiguous and irregular. The described manifestations resulting from discontinuation of the combination treatment is considered to be a warning about the risk of physical dependence on the drug combination.

[A pharmacological analysis of the mechanism of action of ethosuximide]. / Farmakologicheskii analiz mekhanizma deistviia étosuksimida.

Ethosuximide is one of the means of treatment of minor epilepsy but hardly any data on its mechanism of action are available in the literature. Anticonvulsant agents are known to bring about changes in the functions and in the interaction between some of the mediator systems within the central nervous system. An assessment of the status of neuromediator systems can be made on the basis of the response of isolated smooth muscle strips to the action of agonists and antagonists of various receptors. It was found by the pharmacological analysis of isolated strips from the rat stomach (antrum and corpus strips), the seminal duct and the cervical vein that ethosuximide induces a reduction in the physical contractile activity and the tone of smooth muscle preparations. Smooth muscle relaxation caused by ethosuximide is not blocked by different receptor inhibitors such as dihydroergotamine, propranolol, atropine, chlorpromazine, haloperidod and indomethacin. Ethosuximide causes a significant reduction in the physical contraction of smooth muscles produced by potassium chloride depolarization, with a stronger impact on the subsequent tonic contraction caused by calcium ions. A reduction in the potassium content of the solution has no effect on the nature of the action of ethosutimide. It is thus assumed that the probable mechanism of action of ethosuximide consists in lowering calcium transport since the inhibitors of calcium transport sodium nitroprusside and verapamil intensify the blocking effect of ethosuximide on smooth muscle contractile activity.

On octanoic acid-induced hyperventilation--implications for hepatic encephalopathy and Reye's syndrome.

Medium chain fatty acid sodium octanoate was infused into rabbits as a 0.2 M solution over 4 h resulting in blood and brain octanoate levels of 200-800 mumol/l. The infused animals developed marked hyperventilation leading to a mild respiratory alkalosis. Additionally, octanoate infusion brought about hyperammonemia and hyperlactate acidemia. Another group of rabbits also infused with octanoate but pretreated with indomethacin (10 mg/kg b.wt.) developed neither hyperventilation nor hyperammonemia. Therefore, the conclusion made was that octanoate causes the above mentioned disorders through stimulation of prostaglandin synthesis and especially the PGE2 synthesis. Patients with hepatic encephalopathy and Reye's syndrome have elevated levels of plasma octanoate. The present study suggests that octanoate might be the cause for both the hyperventilation and hyperammonemia observed in patients with hepatic encephalopathy and Reye's syndrome.