Epilepsies GABA transmission

In CONCLUSION, epilepsy is a term used to describe a variety of recurrent symptoms which result from the synchronous or sustained discharge of a group of neurons. It is not clear which specific abnormality in synaptic function is associated with epilepsy, but there is some evidence that an impairment of inhibitory transmission in the neocortex and hippocampus may be primarily involved. The possible causative role of GABA is supported by the fact that many clinically useful anticonvulsants facilitate GABA transmission. Other anticonvulsants may owe their efficacy to their ability to stabilize cation movements across neuronal membranes and /or to affect the phosphorylation of membrane proteins. 

Carbamazepine is licenced as an alternative to lithium for prophylaxis of bipolar affective disorder, although clinical trial evidence is actually stronger to support its use in the treatment of acute mania. Carbamazepine appears to be more effective than lithium for rapidly cycling bipolar disorders, i.e. with recurrent swift transitions from mania to depression. It is also effective in combination with lithium. Its mode of action is thought to involve agonism of inhibitory GABA transmission at the GABA-benzodiazepine receptor complex (see also Epilepsy, p. 417). 

Benzodiazepines. Several BZs have anticonvulsant activity and ate used for the treatment of epilepsy producing their anticonvulsant actions via interactions with the GABA /BZ receptor complex to enhance inhibitory GABAergic transmission (1). The anticonvulsant actions of the BZs tend to tolerate upon chronic usage in six months, and BZs also lead to withdrawal symptomatology. Other side effects include sedation, ataxia, and cognitive impairment. 

Epilepsy is caused by abnormal high-frequency firing of neurons, either in the whole of the cerebral cortex (generalized epilepsy) or in discrete areas of the cerebral cortex (partial epilepsy). The abnormal activity may be due to increased excitatory neuronal transmission, possibly involving abnormal sodium ion channels or decreased inhibitory transmission, possibly due to abnormality at GABA receptors. Certainly, most antiepileptic drugs either block sodium ion channels or enhance the action of GABA or both. 

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