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Endogenous anticonvulsant substances
Abstract:
Epileptic seizures will normally arrest abruptly and spontaneously, and the brain will remain refractory to further seizures for some time thereafter. This paper reviews the possible mechanisms underlying this seizure arrest and refractoriness. The data suggests that neuronal fatigue is not involved in either of these processes, whereas the role of ions and excitatory systems are unclear. Rather, seizure arrest and refractoriness may come about by the seizure-induced release and/or activity of multiple endogenous anticonvulsant substances. The spontaneous arrest of the seizure may involve the purine adenosine, in addition to other unknown mechanisms. Seizure refractoriness involves multiple systems, the most important of which, on the available evidence, are prostaglandins and opioid peptides and possibly benzodiazepine systems, although other neuropeptides and the purines may also be involved. The implications of these conclusions to anti-epileptic drug development and status epilepticus are discussed.
Insights
Epileptic seizures stop spontaneously due to endogenous anticonvulsant substances, not neuronal fatigue. These substances, including adenosine, prostaglandins, and opioids, also prevent further seizures, impacting epilepsy drug development.
Area of Science:
- Neuroscience
- Pharmacology
- Epileptology
Background:
- Epileptic seizures typically cease abruptly and spontaneously.
- Following a seizure, the brain exhibits a period of refractoriness to subsequent seizures.
Purpose of the Study:
- To review potential mechanisms of seizure arrest.
- To investigate the processes underlying post-ictal brain refractoriness.
Main Methods:
- Literature review of existing data on seizure arrest and refractoriness.
- Analysis of proposed endogenous anticonvulsant mechanisms.
Main Results:
- Neuronal fatigue does not appear to be involved in seizure arrest or refractoriness.
- Seizure arrest may involve the purine adenosine and other unknown factors.
- Seizure refractoriness involves prostaglandins, opioid peptides, benzodiazepine systems, neuropeptides, and purines.
Conclusions:
- Endogenous anticonvulsant substances, released during seizures, are key to both arrest and refractoriness.
- Adenosine, prostaglandins, and opioid peptides are significant contributors.
- Findings have implications for developing new anti-epileptic drugs and managing status epilepticus.