Epilepsy

C12H12N2O3. White crystals, m.p. 174°C. Prepared by condensing the ethyl ester of phenylethylmalonic acid with urea. It is a more active hypnotic than barbitone. It and its sodium salt - soluble phenobarbitone - are used as sedatives and in treating epilepsy. 

Cj jH,2N202. Used as its sodium salt, which is a white hygroscopic powder. Unstable, readily absorbing carbon dioxide and liberating phenytoin. Made by treating a-bromodi-phenylacetylurea with alcoholic ammonia. It has a mild hypnotic and strong anticonvulsant action, and is used in the treatment of grand-mal and focal epilepsy. 

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. 

Commission on Classification and Terminology of the International League Against Epilepsy, Epilepsia 22, 289—501 (1981). 

Fohc acid is safe, even at levels of daily oral supplementation up to 5—10 mg (97). Gastrointestinal upset and an altered sleep pattern have been reported at 15 mg/day (98). A high intake of foHc acid can mask the clinical signs of pernicious anemia which results from vitamin deficiency and recurrence of epilepsy in epileptics treated with dmgs with antifolate activity (99). The acute toxicity (LD q) is approximately 500 and 600 mg per kg body weight for rats and mice, respectively (100). 

The success of quinine inspired the search for other antimalarials. The greatest impetus for the development of synthetic dmgs came this century when the two World Wars intermpted the supply of cinchona bark to the combatants. A stmcturally related 4-quinolinemethanol is mefloquine (65, Lariam [51773-92-3]) which now serves as an effective alternative agent for chloroquine-resistant P. falciparum. This is a potent substance that requires less than one-tenth the dose of quinine to effect cures. There are some untoward side effects associated with this dmg such as gastrointestinal upset and dizziness, but they tend to be transient. Mefloquine is not recommended for use by those using beta-blockers, those whose job requires fine coordination and spatial discrimination, or those with a history of epilepsy or psychiatric disorders. A combination of mefloquine with Fansidar (a mixture of pyrimethamine and sulfadoxine) is known as Fansimef but its use is not recommended. Resistance to mefloquine has been reported even though the compound has not been in wide use. 

Because alcohol intoxication may be simulated by many pathologic conditions, including diabetic acidosis, the postconvulsive depression of epilepsy, uremia, head injuries, and poisonings by any other central nervous depressant and some stimulants (280), a diagnosis of acute alcoholism should not be made casually chemical testing of blood, urine, or expired air is always desirable. 

The anticonvulsant primidone (1035) resembles phenobarbital but lacks the 2-oxo substituent. It was introduced in 1952 and has remained a valuable drug for controlling grand mal and psychomotor epilepsy. As might be expected, primidone is metabolized to yield phenobarbital (1034 X = 0) and C-ethyl-C-phenylmalondiamide (1036), both of which have marked anticonvulsant properties however, primidone does have intrinsic activity and an appropriate mixture of its metabolites has only a fraction of its activity (73MI21303). Primidone may be made in several ways, of which desulfurization by Raney nickel of the 2-thiobarbiturate (1034 X = S) or treatment of the diamide (1036) with formic acid (at 190 °C) seem to be the most satisfactory (54JCS3263). 

Bromide therapy introduced by Lacock as a sedative and anticonvulsant for treatment of epilepsy... 

Formal oxidation of pyrrolidine to the succinimide stage affords a series of compounds used as anticonvulsant agents for treatment of seizures in petit mal epilepsy. Knoevnagel condensation of benzaldehyde with ethyl cyanoacetate affords the unsaturated ester, 9. Conjugate addition of cyanide ion leads to the di-nitrile ester (10). Hydrolysis in mineral acid affords the succinic acid (11), presumably by decarboxylation of the intermediate tricarboxyllie acid. Lactamization with methylamine gives phensuximide (12). ... 

Epilepsy, grand mal. A disorder resulting in occasional loss of consciousness and violent uncontrolled contraction of the muscles. 

Epilepsy, petit mal. Similar to grand mal except that muscle manifestations are either absent or confined to occasional jerks. 

Fall-schinn, m. parachute, -schirmleuchte, /. parachute flare, -silber, n. deposited silver, -sucht, /. epilepsy, -tiir, /. trapdoor. 

Absence Epilepsies are a group of epileptic syndromes typically starting in childhood or adolescence and characterized by a sudden lack of attention and mild automatic movements for some seconds to minutes. Absence epilepsies are generalized, i.e. the whole neocortex shifts into a state of sleep-like oscillations. 

Epilepsy is a chronic neurological disorder that affects about 0.6-0.8% of the general population worldwide. The clinical hallmark of epilepsy is... 

Primary generalized seizures are also heterogeneous with respect to their clinical features. Such seizures can impose as absence epilepsy, which is characterized by a brief interruption of consciousness due to highly synchronized neuronal activity involving thalamocortical networks without increases in neuronal firing rate. On the other hand, tonic-clonic convulsions with loss of consciousness are often also primarily generalized. 

Both focal and generalized epilepsies are heterogeneous with respect to their etiology and the principles of therapy. 

In focal epilepsies a number of functional and morphological changes are observed which may act in concert to support enhanced excitability. Such changes have been intensively investigated in order to develop targets for drug design. 

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. 

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