Epilepsies neurotransmitters

How the different neurotransmitters may be involved in the initiation and maintenance of some brain disorders, such as Parkinson s disease, epilepsy, schizophrenia, depression, anxiety and dementia, as well as in the sensation of pain, is then evaluated and an attempt made to see how the drugs which are used in these conditions produce their effect by modifying appropriate neurotransmitter function (section C). The final section (D) deals with how neurotransmitters are involved in sleep and consciousness and in the social problems of drug use and abuse. 

Cortical function is modulated by many other neurotransmitters. However, their role in the pathophysiology of epilepsy and in the action of antiepileptic drugs is not yet well known. 

Baghdoyan, H. A. Lydic, R. (2002). Neurotransmitters and neuromodulators regulating sleep. In Sleep and Epilepsy The Clinical Spectrum, ed. C. W. Bazil, pp. 17 44. New York, NY Elsevier Science. 

Glutamate that is a major neurotransmitter in the mammalian nervous system not only plays a role in the development of the brain and learning but is also a potent neurotoxin when present in excess at synapses (Plaitakis and Shashidharan, 2000 Rausch et ah, 2006). Glutamate excitotoxicity has been shown to contribute to neuronal degeneration in acute conditions such as stroke, epilepsy, h) oglycemia, and chronic... 

Too Much Neurotransmission. Other mental illnesses result from too much neurotransmission (i.e., overactivity) of certain brain circuits. One example may be psychosis, for example, hallucinations and delusions that have been hypothesized to result from excessive transmission of the neurotransmitter dopamine in certain pathways. In some cases, the transmission becomes so excessive that it kills the nerve cell, a phenomenon called excitotoxicity. This process is believed to occur in some patients with epilepsy and in those with Huntington s disease. 

McNamara JO, Bonhaus DW, Crain BJ, Gellman RJ, Shin C (1987) Biochemical and pharmacological studies of neurotransmitters in the kindling model. In Neurotransmitters and epilepsy. Jobe PC and Laird HE (Eds) Clifton, NJ, Humana 115-160... 

Vigabatrin is a new antiepileptic for use in epilepsy unresponsive to other therapy. It is an irreversible inhibitor of GABA-transaminase, the enzyme responsible for inactivation of the neurotransmitter GABA and it has shown efficacy against partial and secondarily generalized seizures. The principal unwanted effects are psychiatric disorders, including depression and psychosis, in a small number of patients. 

Excitatory neurotransmitters also may be involved in the appearance of epilepsy, since the bursting activity typically seen during epileptic discharges may be due in part to the action of glutamate acting on A-methyl-o-aspartate (NMDA) receptor channels to produce depolarization. It is likely that a major part of the anticonvulsant activity of felbamate involves blockade of the NMDA receptor. Table 32.2 summarizes the most likely mechanism of action associated with available anticonvulsant drugs. 

Complexity of inhibition of PLP-dependent enzymes is highlighted by detailed investigations on the inhibition of y-aminobutyric acid aminotransferase (GABA-AT), the enzyme responsible for the degradation of y-aminobutyric acid (GABA), one of the major inhibitory neurotransmitters in the mammalian central nervous system. Inhibition of GAB A-AT results in an increased concentration of GABA in the brain and could have therapeutic applications in neurological disorders (epilepsy, Parkinson disease, and Alzheimer disease). 

Taurine (2-aminoethanesulfonic acid 4.235) is an inhibitory neurochemical that probably acts primarily as a neuromodulator rather than a neurotransmitter. It is formed from cysteine, and its accumulation can be prevented by the cardiac glycoside ouabain. Although receptor sites and specific actions cannot be elucidated without an antagonist, taurine has been implicated in epilepsy and, potentially, in heart disease. There are a large number of physiological effects attributed to taurine, among them cardiovascular (antiarrythmic), central (anticonvulsant, excitability modulation), muscle (membrane stabilizer), and reproductive (sperm motility factor) activity. Analogs of taurine, phthalimino-taurinamide (4.236) and its iV-alkyl derivatives, are less polar than taurine and are potent anticonvulsant molecules. 

It is a benzodiazepine useful in the treatment of petitmal epilepsy, myoclonic seizures and infantile spasms. It is used in the treatment of petitmal epilepsy not responding to ethosuximide and sodium valproate. Clonazepam and diazepam act by increasing the effectiveness of the inhibitory neurotransmitter GABA, within the central nervous system. 

Webster RA. The epilepsies. In Webster RA, ed. Neurotransmitters, Drugs and Brain Function. New York John Wiley and Sons 2001. 

Whereas the genetic and kindling models have been widely used to investigate possible neurotransmitter defects that cause different types of epilepsy, rodent models in which seizures are induced by electroshock, or by convulsant drugs such as pentylenetetrazol (also called pentetrazol, leptazol), picrotoxin or bicuculline, are mainly used in screening procedures to identify potential anticonvulsants. 

Of the various amino acid neurotransmitters which have been implicated in epilepsy, the inhibitory transmitter glycine has been shown to be present in normal concentrations, or even slightly elevated, in the vicinity of the... 

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