Epilepsy inhibition

Altered synaptic properties Numerous changes in the properties of inhibitory (GABAergic) and excitatory (glutamatergic) synapses have been reported. While the simple adage of an imbalance between inhibitory and excitatory neurotransmission in epilepsy is not generally applicable, some forms of inhibition are lost or impaired in epilepsy. Likewise, an increased function of glutamate receptors has been demonstrated in some brain areas. 

NTs it is now appropriate to consider what evidence there is for a malfunction of NT activity in epilepsy, particularly in those responsible for primary excitation and inhibition, i.e. the amino acids. Before doing so the epileptogenesis of absence seizures (petit mal) justifies separate consideration. 

A number of studies have shown that adenosine inhibits neuronal firing both in vitro and in vivo and is itself released during intense neuronal activity. It can protect against PTZ seizures in rodents while the antagonist theophylline is proconvulsant. No clear picture of its role in human epilepsy has emerged. 

Irrespective of the cause of epilepsy, the spread of seizure activity will be attenuated by either decreasing the excitation or increasing the inhibition of neurons. This may be achieved in a number of ways, either directly by... 

Introduced initially for absence seizures, this drug is now known to be effective in and used to treat tonic lonic seizures and most types of epilepsy. It was found to inhibit GABA transaminase and so elevate GABA concentrations and inhibition. This is achieved, however, over a slower time-course than its anti-seizure effect, especially experimentally, which is now thought to be due to its phenytoin-like, use-dependent block of sodium channels. Since, unlike phenytoin, the full effect of valproate takes some weeks to develop, its slower effect on GABA metabolism and activity should not be ignored. 

This is not really a treatment but there is a view that glial cells can protect against seizures since the enzyme systems they possess (e.g. Na-K+ATPase and carbonic anhydrase) facilitate the regulation of ion movements and reduce the spread of seizures. Certainly ageing, a fatty diet, and phenytoin itself increase glial cell count while decreasing seizure susceptibility. In fact inhibition of carbonic anhydrase and the production of bicarbonate was one of the first treatments for epilepsy and a recent discovery that under certain circumstances intracellular bicarbonate can depolarise neurons has created a fresh interest in it. 

Epilepsy Electrically evoked convulsions in mice Inhibits convulsions [66]... 

Buhl, E. H., Otis, T. S. and Mody, I. Zinc-induced collapse of augmented inhibition by GABA in a temporal lobe epilepsy model. Science 271 369-373,1996. 

Gabapentin inhibits high-voltage activated Ca channels and elevates human brain GABA levels. It is a second-line agent for patients with partial seizures who have failed initial treatment. It may also have a role in patients with less severe seizure disorders, such as new-onset partial epilepsy, especially in elderly patients. 

GABA GABAa Rat brain Alcoholism, CNS, anesthesia, epilepsy, anxiety, depression, Parkinson s disease, pain, migraine, respiratory gastrointestinal, diabetes, obesity Synaptic inhibition, decrease in neuronal excitability increase in cellular chloride influx, neuroprotection, sedation/hypnosis, anticonvulsant activity muscle relaxation... 

Klassen A, Glykys J, Maguire J, Labarca C, Mody 1, Boulter J (2006) Seizures and enhanced cortical GABAergic inhibition in two mouse models of human autosomal dominant nocturnal frontal lobe epilepsy. Proc Natl Acad Sci U S A 103 191152-191157 KUnk R, de Kerchove d Exaerde A, Zoli M, Changeux IP (2001) Molecular and physiological diversity of nicotinic acetylchohne receptors in the midbrain dopaminergic nuclei. J Neurosci 21 1452-1463... 

Some drags block sodium channels, while others act on the GABA system. They enhance the GABA-dependent CNS inhibition. They also change the innacellular ratio of calcium and potassium ion concentrations, and block the A-methyl-o-aspartate (NMDA) receptor responsible for high-frequency discharges that appear during epilepsy. 

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