GABA valproate

The oxa2ohdinedione trimethadione [127-48-0] C H NO (50), at one time the dmg of choice for the treatment of absence sei2ures, has been replaced by ethosuximide (41) and valproate (49). (50) has a distinct profile from that of phenytoin but causes photophobia and night blindness in approximately 30% of the patients taking it and has the CNS and sedative properties seen for other anticonvulsants together with moderate neutropenia, hepatitis, and skin rashes (13). Trimethadione does not appear to produce its effects via modulation of GABA-mediated responses. 

Sodium valproate GM PM 6 also 1 Inhibition of GABA metabolism... 

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. 

Sodium valproate Inhibits GABA 600-1200 mg/day Neurologic disturbances, Variable efficacy seen in Cushing s... 

Use in combination with other drugs (e.g, anti-psychotics, lithium, valproate) for the acute treatment of mania or mixed episodes. Use as a short-term adjunctive sedativehypnotic agent. Binds to the benzodiazepine site and augments the action of GABA/, by increasing the frequency of Cl" channel opening which causes hyperpolarization (a less excitable state) and inhibits neuronal firing. 

Hechler, V., Ratomponirina, C., and Maitre, M. (1997) Gamma-hydroxybutyrate conversion into GABA induces displacement of GABAb binding that is blocked by valproate and etho-suximide. J. Pharmacol. Exp. Ther. 281,753-760. 

The mechanism of action of valproate is complex and still the subject of uncertainty. The drug appears to act by enhancing GABAergic function. Thus it increases GABA release, inhibits catabolism and increases the density of GABA-B receptors in the brain. There is also evidence that it increases the sensitivity of GABA receptors to the action of the inhibitory transmitter. Other actions that may contribute to its therapeutic effects include a decrease in dopamine turnover, a decrease in the activity of the NMDA-glutamate receptors and also a decrease in the concentration of... 

Drugs acting on GABA/glutamate - hypnotics/anxiolytics barbiturates, benzodiazepines, chlormethiazole, chloral derivatives, baclofen - anticonvulsants phenobarbitone, primidone, phe-nytoin, sodium, valproate, carbamazepine - alcohol, phencyclidine, ketamine... 

As with several other AEDs, it is difficult to ascribe a single mechanism of action to valproic acid. This compound has broad anticonvulsant activity, both in experimental studies and in the therapeutic management of human epilepsy. Valproic acid has been shown to block voltage-dependent sodium channels at therapeutically relevant concentrations. In several experimental studies, valproate caused an increase in brain GABA the mechanism was unclear. There is evidence that valproate... 

Loscher, W. (1993) In vivo administration of valproate reduces the netve tetminal (synaptosomal) activity of GABA aminotransferase in discrete btain ateas of tats. Neurosci Lett 160 177-80. 

Emrich HM, von Zerssen D, Kissling W, et al Effect of sodium valproate on mania the GABA hypothesis of affective disorders. Archiv fur Psychiatrie und Nervenkrankheiten 229 1-16, 1980... 

Sodium valproate increases the levels of GABA in the brain and increases the... 

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. 

Valproic acid. Although its exact mechanism of action remains uncertain, valproic acid (also valproate sodium, or valproate) may inhibit sodium and/or calcium channel function and perhaps thereby boost GABA inhibitory action as well as reduce glutamate excitatory action (Fig. 7—23). A unique and patented pharmaceutical formulation of valproic acid, called Depakote, reduces gastrointestinal side effects. 

FIGURE 7-23. Shown here is an icon of valproic acid s pharmacologic actions. By interfering with calcium channels and sodium channels, valproate is thought both to enhance the inhibitory actions of gamma aminobutyric acid (GABA) and to reduce the excitatory actions of glutamate. 

The actions of anticonvulsants at the cellular level are complex and include facilitation of inhibitory feedback mechanisms, membrane stabilization and changes in synaptic transmission to reduce excitatory transmission. Of these various possibilities, it is widely accepted that anticonvulsants enhance GABA-mediated inhibitory processes. Such a mechanism has been clearly demonstrated for the benzodiazepines, barbiturates, diphenylhydantoin and sodium valproate. 

Electrophysiological studies show that benzodiazepines, barbiturates and sodium valproate facilitate GABAergic transmission in the animal brain. Further evidence comes from studies on the GABA-benzodiazepine receptor complex, the order of potency of a series of benzodiazepines to displace [3H] diazepam from its receptor site being clearly correlated with the antagonism of pentylenetetrazol seizures, but not with electroconvulsive seizures. However, most classes of anticonvulsants appear to facilitate... 

The precise mechanism of action of valproate in facilitating GABA transmission is still uncertain. There is evidence that the drug can facilitate... 

GABA synthesis, probably by inhibiting GABA transaminase activity, but the dose of drug necessary to achieve this effect is very high and not relevant to the clinical situation. One possibility is that valproate desensitizes GABA autoreceptors and thereby facilitates the release of the transmitter. 

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