ABSTRACT
The pharmacodynamics of those benzodiazepines exerting an antiepileptic effect are described. These drugs act as positive allosteric modulators of the GABAA receptor and potentiate the inhibitory effect of presynaptically released GABA on diverse neurons, including dopaminergic and noradrenergic neurons located in the brainstem, hippocampus, and prefrontal cortex. Among the endogenous benzodiazepines, the most important endozepines are mentioned, and the interaction of these endozepines with the benzodiazepine-binding site at the GABAA receptor and their roles in generalized epilepsy are also pointed out. When an epileptic seizure becomes a status epilepticus, benzodiazepines lose their antiepileptic effects as a consequence of the GABAA and NMDA glutamate receptor trafficking. For this reason, in clinical practice, it is recommended to combine the benzodiazepines diazepam, lorazepam, or midazolam with an NMDA receptor antagonist, such as ketamine. Neural networks involved in generalized epilepsy and located in the hippocampus, thalamus, and cerebral cortex are depicted. The pharmacokinetics of benzodiazepines exerting an antiepileptic effect (clonazepam, clobazam, diazepam, lorazepam, midazolam) are also described in detail. These drugs can be administered as an intravenous, oral, intranasal, or rectal route. The indications and the appropriate doses of benzodiazepines are also mentioned as well as their adverse effects.
