Antiepileptic drug therapy in the twenty first century.

In the last 25 years, particularly the last decade, there have been many advances relating to all aspects of epilepsy i.e. pathophysiology, diagnosis, pharmacotherapy and surgical interventions. Noteworthy has been the progress in terms of understanding of the established antiepileptic drugs (AEDs) and introduction of several newer agents developed rationally, on the basis of now available information on the biochemical changes in the epileptic brain. Data is accumulating regarding the use of newer agents but they still need to stand the test of time. Many of the newer AEDs may offer a better tolerability because of favorable pharmacokinetic characteristics and minimal drug interactions. However, serious adverse events have been associated with felbamate and lamotrigine already and for other newer agents reliable and accurate data needs to be generated.

Influence of adenosine agonists and antiepileptic drugs on theophylline-induced seizures in rats.

Seizures is a major toxicity of theophylline. The mechanism of theophylline-induced seizures is not known, but antagonism at adenosine receptors may be a possibility. The effect of pretreatment with different doses of adenosine (100, 500 and 1000 mg/kg, i.p.), and the adenosine A1 receptor agonist N6-cyclopentyladenosine (CPA), 1, 5 and 10 mg/kg, i.p., was studied against seizures induced by theophylline in rats. Both these drugs, at all dose levels tested, failed to protect theophylline seizures. Thus adenosinergic system is unlikely to be involved in mediating the convulsant action of theophylline. On the other hand, the conventional antiepileptic drugs, i.e. diazepam (4 mg/kg), sodium valproate (300 mg/kg) and phenobarbitone (50 mg/kg), but not carbamazepine, afforded some protection. The modification of course of seizures, by the antiepileptic drugs suggests the involvement of some other alternate mechanism in theophylline-induced seizures.

Adenosinergic system as an endogenous anticonvulsant mechanism.

The treatment of epilepsies remains far from adequate primarily due to inadequate understanding of the pathophysiology of seizures. The conventional approach for research into epilepsy has been study of factors responsible for initiation of seizures. However, now attention is being drawn to the spontaneous and abrupt arrest of seizures which suggests a distinct possibility of activation of an endogenous anticonvulsant mechanism(s), which may be targeted in future for controlling seizures. Of the various endogenous anticonvulsant mechanisms, the concept of an endogenous anticonvulsant substance has gained much experimental support and, many potential candidates have been postulated. Of these adenosinergic system appears to be the most promising. This review discusses the possible role of adenosinergic system in seizures, in relation to the available antiepileptic drugs and its therapeutic implications.

Effect of theophylline on diazepam and sodium valproate protection in pentylenetetrazole - kindled seizures in rats.

Theophylline is well known for its convulsant and proconvulsant action. Some experimental studies also suggest that theophylline and other methylxanthines may impair the protection of antiepileptic drugs. The interaction of theophylline and the antiepileptic drugs diazepam and sodium valproate was studied in pentylenetetrazole (PTZ) - kindled seizures in rats. Pretreatment with both diazepam 4 mg/kg and sodium valproate 300 mg/kg, i.p., showed protection against PTZ kindled seizures. Theophylline, 50 mg/kg, i.p., when given before the antiepileptic drugs, failed to reverse their protection. Since theophylline has an adenosine receptor antagonist activity which may be responsible for its convulsant potential, the results indicate non-involvement of adenosinergic mechanisms in the mechanisms of actions of these antiepileptic drugs.

Anaesthetic steroids--a review.

Steroids produce anaesthesia besides producing the well known metabolic and hormonal effects. A number of anaesthetic steroids have been synthesized and tried clinically. Hydroxydione, althesin, minaxolone and pregnanolone are among those studied in detail. They act through GABAergic mechanism and are known to be advantageous over barbiturates.