Molecular mechanisms of antiseizure drug activity at GABAA receptors
| Autor: | Jr. L. John Greenfield |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Ganaxolone
Antiepileptic drugs Clinical Neurology Loreclezole Pharmacology Article Felbamate chemistry.chemical_compound Benzodiazepines GABA receptor Seizures medicine Animals Humans Inhibition Epilepsy GABAA receptor Retigabine Allopregnanolone General Medicine Receptors GABA-A chemistry Neurology Barbiturates GABAergic Anticonvulsants Neurology (clinical) Neuroscience Chloride channel medicine.drug |
| Zdroj: | Seizure. 22(8):589-600 |
| ISSN: | 1059-1311 |
| DOI: | 10.1016/j.seizure.2013.04.015 |
| Popis: | The GABAA receptor (GABAAR) is a major target of antiseizure drugs (ASDs). A variety of agents that act at GABAARs s are used to terminate or prevent seizures. Many act at distinct receptor sites determined by the subunit composition of the holoreceptor. For the benzodiazepines, barbiturates, and loreclezole, actions at the GABAAR are the primary or only known mechanism of antiseizure action. For topiramate, felbamate, retigabine, losigamone and stiripentol, GABAAR modulation is one of several possible antiseizure mechanisms. Allopregnanolone, a progesterone metabolite that enhances GABAAR function, led to the development of ganaxolone. Other agents modulate GABAergic “tone” by regulating the synthesis, transport or breakdown of GABA. GABAAR efficacy is also affected by the transmembrane chloride gradient, which changes during development and in chronic epilepsy. This may provide an additional target for “GABAergic” ASDs. GABAAR subunit changes occur both acutely during status epilepticus and in chronic epilepsy, which alter both intrinsic GABAAR function and the response to GABAAR-acting ASDs. Manipulation of subunit expression patterns or novel ASDs targeting the altered receptors may provide a novel approach for seizure prevention. |
| Databáze: | OpenAIRE |
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