And yet, notwithstanding theoretical prerequisites, glycine proved to be an inefficient anti-convulsive drug. In spite of the popularity of the glutamate hypothesis in the disease concerned, the literature does not carry reports on a favorable effect of the amino acid (3).

All this calls into question not only the "glutamate" hypothesis but the above interpretation of the glycine action mechanism as well.

The following natural anti-convulsive drugs are used in clinical practice: glutamic acid, tryptophan, cerebrolysine, aminolone (g-aminobutyric acid).

Therapeutic effectiveness of the enumerated drugs is widely discussed in the literature (3). We have tested and introduced 4 amino acid drugs possessing an anti-convulsive effect.

The action mechanism is different. Aminovil, the most widely used drug, blocks absorption of g-aminobutyric acid by astrocytes and simultaneously enhances the capture of dicarboxilic amino acids. This results in a changed ratio of the inhibition and excitement mediators in neurocytes and glial cells.

The testing revealed that the drug had not only an anti-depressive but also neotropic effect, this is why it was employed in the treatment of not only epilepsy, but also in the therapy of cerebrovascular illnesses, including chronic cerebrovascular insufficiency. Daily dosages were 1-2 g. The therapeutic effect occurred on the 2nd-4th day. The drug was frequently used in combination with Glucaprim.

In epileptology, the action of this drug is universal. The therapeutic effect was recorded in all forms of the disease, including Jackson’s seizures.

A manifest anti-diuretic effect is a unique feature of the drug. This is the reason why Aminovil was largely applied in hydrocephaly patients; in terms of therapeutic efficiency, it outperforms other diuretic drugs such as Diacarb.

Trevit acts in much the same way. Its diuretic effect is less pronounced, however, and, in case of prolonged administration, it may cause side effects and complications.

Evit, an amino acid compound, was used only to stop nocturnal attacks. It was applied for long periods in two-week courses of treatment with 10-day intervals. The action mechanism: serotonin exchange correction and suppression of LPO processes.

Concluding a review of the drugs that indirectly confirm the leading role of the "glutamate hypothesis" in the mechanism of the decay of nerve cells, one more group of drugs, glutamic acid antagonists (of the rilosol type), should be singled out the testing of which is performed in a number of clinics in the world. As yet, positive results are identical and little conclusive.

Thus, the administration of a daily dosage of 100 g rilosol in ALS patients could prolong their life time by 12 months (7).

The "arginine" hypothesis advanced in the early 90s has not won acceptance either. A lot of therapeutic drugs are still being clinically tested. And, while in cardiology and gastroenterology the role of arginine metabolites in the pathogenesis of a number of diseases is considered proven, clinical neurology is still making its first steps in this direction.

NO (or relaxation factor) is called a substance of the century. It is a proven fact that the absolute majority of vascular drugs produce a therapeutic effect by changing the NO level in the smooth muscle cells (14).

Arginine amino acid is a metabolite source in the tissues whereas NO is formed in two stages (12).

The first reaction catalyzed by NO-synthetase produces hydroxyarginine, a rather stable compound that, under the influence of an unknown enzyme (the second reaction), is disintegrated into nitric oxide and citrulline.

The NO-synthetase activity and, hence, the speed of nitric oxide formation in the tissues are controlled by the calcium level and determined by the functional state of NMDA receptors. In its turn, nitric oxide that also activates the cGMP-synthetase triggers off a cascade of reactions that lead to a decrease in the cation level in the cells by suppressing the inositide cycle (4).

It should be pointed out that most NO effects in neurocytes are due to a changed cGMP-synthetase activity. The highest enzyme activity was recorded in the cerebellum, the region of the reticular cerebral trunk formation, the subcortical structures as well as the occipital lobule of the cerebral hemispheres. There is clear evidence that in some cerebral structures NO act as a kind of neuromediator (11).

It should not be overlooked, however, that a large amount of NO represents a toxic agent. The duration of the radical is several seconds. But if superoxide radicals in the cell are in excess, a combined long-living toxic peroxinitrate anion, a powerful initiator of LPO processes, is formed (6).

Unlike nitric oxide, peroxynitrate anion stimulates the capture of calcium by mitochondria dissociating tissue breath and phosphorylation processes which eventually produces a drop in the energetic potential of the nerve cells with ensuing consequences.

According to the literature, genetically determined superoxide dismutase insufficiently occurs in some degenerative diseases, in particular, in ALS patients (13).

In an experiment, a restriction of NO-synthetase activity by injecting inhibitors (N-nitro-L-arginine) produced a favorable effect. Thus, 2-3 injections of the drug (in subcortical degenerations) resulted in a decreased progression of the pathologic disorder. In another group of animals with experimental cerebral ischemia a significant reduction of the size of foci was reported when an NO-synthetase inhibitor was previously injected (11, 6).

There is still another risk of producing enzyme hyperactivation consequences: instead of the end product, NO, the cell may accumulate an excessive amount of an intermediate product of the reaction, Nw-hydroxy-L-arginine which is a potent cytostatic agent that inhibits the key DNA synthesis enzymes (8).

Thus, the literature corroborates the important role played by nitrogen oxide in the pathogenesis of nervous system diseases. Unfortunately, laboratory research does not make it possible to determine the metabolite content in bioliquids, this is why we have to confirm only indirectly our assumptions regarding disturbed metabolism of this compound. In particular, we often determine the content of nitrites and nitrates, end products of the nitric oxide metabolism. For this purpose, patients were put on a diet without any nitric products after which the content of the nitrate and nitrite level was determined in the blood and liquor of the patients; in this case a set of reagents of the German Merck company was used.

While in healthy persons the nitrate content in 1 ml of cerebrospinal liquid was in the 3-8 mkg range, in ALS patients, irrespective of their age, form and duration of the disease, invariably zero results were recorded. A proved metabolite decrease was also found in parkinsonism, multiple sclerosis patients and in other diseases.

On the basis of the results arrived at it was assumed that an accumulation of intermediate NO-synthetase reaction products occurred in some neurologic illnesses. The process was especially active in ALS patients. Neurovit that represents an amino acid compound was employed to regulate the level of nitrocompound; its intake during 2-3 days at a dosage of 0.5-2.0 g produced not only an essential increase of nitrates in blood and liquor but had a manifest therapeutic effect in many nervous disorders.

Thus, the bulbar syndrome of whatever origin (ALS, consequences of severe cerebral circulation impairment, neuroinfection, etc.) was dealt with by administrating the pharmaceutical preparation during 10-14 days.

And yet the produced therapeutic action dwindled to nothing in a matter of 14-22 days which called for continued drug injection with short 7-12 day intervals. As a result (supervision lasted for 2 years), we could manage to stabilize the pathologic process in patients with central motoneuron involvement.