The New Drugs and the Strategies to Manage Epilepsy

Abstract

After a short historical review of the development of the pharmaceutical treatment of the epilepsies the author reviews some of the possible strategies to manage patients with the different types of epilepsies and epileptic syndromes using the classical drugs. A strategy used by most of the physicians uses Sodium Valproate as the first line drug for almost all patients. This may be replaced by other drugs according to their efficacy against the different types of seizures to be treated whenever VPA has not enough efficacy or isn t well tolerated. On the other hand epileptologists use the different drugs according to the different epilepsies and epileptic syndromes depending on the relative efficacy of each drug available and the possible side effects. He then describes succinctly the better-known new drugs and makes some comments on the coming drugs now in development. Finally he proceeds to include them in the strategies above described. Lamotrigine and possibly Topiramate are good candidates to replace VPA in the one drug strategy. Lamotrigine, Oxcarbamazepine and possibly Gabapentin may be used in the future as 1st line drugs in selected patients. Vigabatrin is already used as one of the better alternatives for West syndrome and Oxcarbamazepine has replaced Carbamazepine in countries where it s available to the public. Some drawbacks have been apparent with these drugs like the hepatic and haematological toxic effect of Felbamate or the apparently irreversible fields constriction provoked by Vigabatrin, which did limit their use.

Isatin and its derivatives: a survey of recent syntheses, reactions, and applications

“…The available antiepileptic drugs (AEDs) show various side effects, such as ataxia, drowsiness, gingival hyperplasia, gastrointestinal disturbances, and megaloblastic anemia, and hence new anti-convulsants with less toxic effects are required. 93,94 The conformational analysis of the well-known AEDs revealed that the essential structural features responsible for interaction with the receptor sites are a hydrogen acceptor/ donor unit (HAD), one electron donor atom (D) and a hydrophobic domain (A) (aryl ring substituted/ unsubstituted). 95,96 Saravanan et al 97 reported the anticonvulsant activity of novel 1-(morpholinomethyl)-3substituted isatin derivatives (42 and 43).…”

Synthesis and Anticonvulsant Activity of Amino Acid-Derived Sulfamides

“…The past decades have witnessed many advances in the development of new strategies for the treatment of epilepsy, mainly focused in the prevention of seizures. The new antiepileptic drugs (AEDs a Abbreviations: MES, maximal electroshock seizure; AEDs, antiepileptic drugs; GABA, γ-amino butyric acid; VPA, valproic acid; PTZ, pentylenetetrazol seizure; CSI, chlorosulfonyl isocyanate; NIH, National Institutes of Health; ADD, anticonvulsant drug development; ASP, anticonvulsant screening project; DIAD, diisopropylazodicarboxylate, PEG, polyethylene glycol; VRL, valrocemide; TPE, time of peak effect. ) presently used provide adequate seizure control in a significant number of the patients. − Unfortunately, it is estimated that up to 30% of the affected people are still resistant to the available medication. , Furthermore, many AEDs have serious side effects, increasing their toxic actions when a lifelong medication is required . As a result, intensive research efforts are being devoted to find new antiepileptic compounds with more selective activity and lower toxicity …”

New Anticonvulsant Agents

“…However, there is a significant group of patients (up to 30%) who are resistant to the available antiepileptic drugs. The long-established AEDs control seizures in 50% of patients developing partial seizures and in 60-70% of those developing generalized seizures [2][3][4][5][6]. Hence, there is an urgent need to develop new AEDs [7].…”