Epilepsy inhibition alteration

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. 

Potschka, H., S. Baltes, and W. Loscher. 2004. Inhibition of multidrug transporters by verapamil or probenecid does not alter blood-brain barrier penetration of levetiracetam in rats. Epilepsy Res 58 85. 

Folic acid can alter the metabolism of phenytoin. In one case folic acid 5 mg/day reduced the serum phenytoin concentration to below the target range, and a breakthrough seizure occurred (25). The Km of phenytoin metabolism was significantly reduced, suggesting competitive inhibition of metabohsm. In another series folic acid reduced the serum concentrations of phenytoin (37). Furthermore, the administration of fohc acid to treat folate deficiency can reduce the beneficial effects of anticonvulsants (38). Rare but serious cases in which this epileptogenic effect of fohc acid has been very pronounced have been reported (39). However, fohc acid is well tolerated by many other patients with epilepsy who require fohc acid. 

Taurine - A glyclne-like, sulphur containing amino acid, taurine (12) is found in reasonably high concentrations throughout the mammalian central nervous system and in heart.In brain, taurine is formed as a result of the decarboxylation of cysteine sulphinic acid (15) to hypotau-rlne (8 ), which in turn is oxidized to form taurine.Like other transmitter candidates, taurine is accumulated and released by brain tissue and the accumulation can be inhibited by ouabain. Clinically, significant alterations in taurine levels may be associated with retinitis pigmentosa, epilepsy, mongolism, and possibly heart disease. 

The incidence of phenytoin toxicity may be increased in the eideriy, or in those patients with hepatic or renal impairment, because of alterations in its pharmacokinetics. Plasma level determinations may be indicated in these cases. Although a role for P-glycoprotein transporter alleles in the development of phenytoin toxicity remains controversial, phenytoin is a robust substrate for the non-ABC efflux transporter RLIP76. Because RLIP76 has been found to be overexpressed in excised human epileptic foci, its action may account for treatment failures conversely, inhibition of transport may cause toxicity (34). There is a 2 to 3% increase in the risk of fetal epilepsy syndrome if the mother is taking phenytoin. Phenytoin is contraindicated in cardiac patients with bradyarrhythmias. Induction of CYP2C19 by ginkgo biloba may increase phenytoin clearance and precipitate serious seizures (35). 

Sloviter, RS (1991b) Permanently altered hippocampal structure, excitability, and inhibition after experimental status epilepticus in the rat the dormant basket cell hypothesis and its possible relevance to temporal lobe epilepsy. Hippocampus, 1 41-66. 

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