A dual mechanism for the anticonvulsant action of aminooxyacetic acid

1976 ◽  
Vol 54 (4) ◽  
pp. 534-540 ◽  
Author(s):  
J. D. Wood ◽  
S. J. Peesker
Keyword(s):  
Isonicotinic Acid ◽  
Acid Hydrazide ◽  
Aminobutyric Acid ◽  
Aminooxyacetic Acid ◽  
Acid Decarboxylase ◽  
Decarboxylase Activity ◽  
Anticonvulsant Action ◽  
Gaba Metabolism ◽  
Dual Mechanism ◽  
The Brain

The intramuscular injection of aminooxyacetic acid (AOAA) into mice elevated the concentration of γ-aminobutyric acid (GABA) in the brain, inhibited glutamic acid decarboxylase activity and delayed the onset of isonicotinic acid hydrazide induced seizures. Analyses of these results and of those obtained previously by the authors and other workers indicated that the anticonvulsant action of AOAA involved two mechanisms. One, involving GABA metabolism, was most effective 6 h after AOAA administration, and the other, not involving GABA, was maximally effective 1.5 h after AOAA injection and was completely absent after 6 h. Depending on the convulsant agent under study, the mechanism of the anticonvulsant action of AOAA was purely of the GABA type, purely of the non-GABA type or a combination of both types.

The Anticonvulsant Properties of Isonicotinic Acid Hydrazide and Associated Changes in γ-Aminobutyric Acid Metabolism

1973 ◽  
Vol 51 (12) ◽  
pp. 959-965 ◽  
Author(s):  
J. D. Wood ◽  
S. J. Peesker
Keyword(s):  
High Pressure ◽  
Acid Metabolism ◽  
Isonicotinic Acid ◽  
Acid Hydrazide ◽  
Aminobutyric Acid ◽  
Isonicotinic Acid Hydrazide ◽  
Acid Decarboxylase ◽  
Anticonvulsant Action ◽  
Drug Mixture ◽  
The Brain

The administration of isonicotinic acid hydrazide and pyridoxine to chicks prior to their being exposed to oxygen at high pressure brought about a delay in the onset of the hyperbaric-oxygen-induced seizures in the birds. The hydrazide was the active anticonvulsant component of the drug mixture but pyridoxine was necessary to prevent seizures induced by the hydrazide itself shortly after its administration. The anticonvulsant action of the drug mixture developed relatively slowly but lasted for several hours and correlated well with concomitant changes in the concentration of γ-aminobutyric acid (GABA) in the brain. No similar correlation was observed between the anticonvulsant action and the activity of either glutamic acid decarboxylase or GABA-α-oxoglutarate aminotransferase.

Effect of L-cycloserine on brain GABA metabolism

1978 ◽  
Vol 56 (1) ◽  
pp. 62-68 ◽  
Author(s):  
J. D. Wood ◽  
S. J. Peesker ◽  
D. K. J. Gorecki ◽  
D. Tsui
Keyword(s):  
Isonicotinic Acid ◽  
Acid Hydrazide ◽  
Acid Decarboxylase ◽  
Dramatic Decrease ◽  
Gaba Metabolism ◽  
Time Period ◽  
Gaba Content ◽  
Brain Gaba ◽  
Prior Administration

The administration of L-cycloserine to mice resulted in a dramatic decrease in the activities of 4-aminobutyrate:2-oxoglutarate aminotransferase (GABA-T) and L-alanine:2-oxoglutarate aminotransferase (ALA-T) in both brain and liver, L-Aspartate:2-oxoglutarate aminotransferase was inhibited only slightly, and brain glutamic acid decarboxylase not at all. Liver ALA-T activity returned to near normal levels within 24 h of L-cycloserine administration whereas liver GABA-T and brain ALA-T activities had returned only halfway to normal levels in the same time period. The recovery in the activity of brain GABA-T was even slower. A consequence of the inhibition of brain GABA-T activity was an elevation in the GABA content of the tissue which was maximal 3 h after L-cycloserine administration and which was still noticeable 8 h after the drug treatment. L-cycloserine was also a potent in vitro inhibitor of brain GABA-T activity. The inhibition was competitive with respect to GABA, the Ki value being 3.1 × 10−5 M. The prior administration of L-cycloserine to mice significantly delayed the onset of isonicotinic acid hydrazide induced convulsions.

ANTICONVULSANT ACTIVITY OF ISONICOTINIC ACID HYDRAZONE DERIVATIVES USING MES, scPTZ AND ROTOROD NEUROTOXICITY MODELS

2018 ◽  
pp. 16-22
Author(s):  
Sinha R ◽  
Singh UVS ◽  
Khosa RL ◽  
Jain J
Keyword(s):  
Melting Point ◽  
Side Effects ◽  
Anticonvulsant Activity ◽  
Capillary Tube ◽  
Isonicotinic Acid ◽  
Acid Hydrazide ◽  
Isonicotinic Acid Hydrazide ◽  
Glass Capillary ◽  
Glass Capillary Tube ◽  
The Brain

Epilepsy is a chronic neurological disorder, involving group of nerve cells, or neurons, in the brain. Many classes of antiepilepticdrugs are being prescribed and used by the stake holders but most of them are associated with serious side effects and toxicity. There is a strongneed of new antiepileptic molecules with less side effects and toxicity. Objective: A series of aryl acid hydrazones of Isonicotinic acid hydrazide(RINH1 -RINH14) were synthesized and evaluated for Anticonvulsant activity. Material and Method: Compounds (RINH1 -RINH14) weresynthesized by refluxing Isonicotinic acid hydrazide with different substituted benzaldehydes/ substituted acetophenones in absolute ethanol.Melting points of all synthesized compounds were monitored by open glass-capillary tube method on Digital Melting point apparatus and areuncorrected. The synthesized compounds were tested for anticonvulsant potential using MES and scPTZ whereas neurotoxicity was determinedusing Rotarod model. Result and Discussion: At 100mg/kg compound RINH10 have shown 29% protection at both 0.5hr and 4.0 time interval.At 300mg/kg and 0.5 hr, compounds RINH4 and RINH10 showed 100% and 50 % protection respectively. Compounds RINH4 and RINH10 havebetter anti MES activity proving that halogens have prominent contribution in Anticonvulsant activity. In scPTZ screen, all synthesized Acidhydrazone (RINH1- RINH14 ) did not show any protection at 30, 100,300 mg/kg , at 0.5 hr and 4.0 hr duration .In rotorod test i.e neurotoxicityscreen, compound RINH5, RINH6 , RINH10 have shown toxicity. Conclusion: The synthesized new molecules were proved to be havinganticonvulsant activity with less signs of neurotoxicity.

scholarly journals THE METABOLISM OF GAMMA AMINOBUTYRIC ACID IN THE LOBSTER NERVOUS SYSTEM

1970 ◽  
Vol 46 (2) ◽  
pp. 290-299 ◽  
Author(s):  
Z. W. Hall ◽  
M. D. Bownds ◽  
E. A. Kravitz
Keyword(s):  
Aminobutyric Acid ◽  
Inhibitory Neurons ◽  
Decarboxylase Activity ◽  
Succinic Semialdehyde ◽  
Gamma Aminobutyric Acid ◽  
Succinic Semialdehyde Dehydrogenase ◽  
Gaba Metabolism ◽  
Semialdehyde Dehydrogenase ◽  
Electrophoretic Behavior ◽  
Inhibitory Transmitter

γ-aminobutyric acid (GABA) is the inhibitory transmitter compound at the lobster neuromuscular junction. This paper presents a comparison of the enzymes of GABA metabolism in single identified inhibitory and excitatory axons from lobster walking legs. Inhibitory axons contain more than 100 times as much glutamic decarboxylase activity as do excitatory axons. GABA-glutamic transaminase is found in both excitatory and inhibitory axons, but about 50% more enzyme is present in inhibitory axons. The kinetic and electrophoretic behavior of the transaminase activity in excitatory and inhibitory axons is similar. Succinic semialdehyde dehydrogenase is found in both axon types, as is an unknown enzyme which converts a contaminant in radioactive glutamic acid to GABA. In lobster inhibitory neurons, therefore, the ability to accumulate GABA ultimately rests on the ability of the neuron to accumulate the enzyme glutamic decarboxylase.

scholarly journals The role of neurotransmitter systems separate the hemispheres of the brain in action the new antiepileptic compounds AGB-31

2013 ◽  
Vol 11 (2) ◽  
pp. 31-35
Author(s):  
Oleg Aleksandrovich Yarosh
Keyword(s):  
Nitric Oxide ◽  
Left Hemisphere ◽  
Glutamic Acid Decarboxylase ◽  
Right Hemisphere ◽  
Reduced Glutathione ◽  
Acid Decarboxylase ◽  
Decarboxylase Activity ◽  
The Right ◽  
The Brain

Compound AGB-31, a monocarbamate derivative, is shown to possess a high antiepileptic activity. The mechanisms of antiepileptic action are connected with significant increase in glutamic acid decarboxylase activity in the left hemisphere of the brain, with trend of the glutamate content decrease in the left hemisphere and the tendency to increase GABA in both hemispheres. AGB-31 significantly (more than 3-fold) increases syntase nitric oxide activity in the left hemisphere and has a tendency to reduce the NO content in both hemispheres. AGB-31 significantly (by 63.4%), reduced glutathione peroxydase activity in the right hemisphere without changing it in the left, with a tendency to increase the activity of glutathione reductase in both hemispheres.

The Possible Involvement of an Amino Acid Decarboxylase in the Stimulation of the Pericardial Cells of Periplaneta by the Corpus Cardiacum

1963 ◽  
Vol 40 (2) ◽  
pp. 343-350
Author(s):  
K. G. DAVEY
Keyword(s):  
Amino Acid ◽  
Isonicotinic Acid ◽  
Isolated Heart ◽  
Acid Hydrazide ◽  
Acid Decarboxylase ◽  
Corpus Cardiacum ◽  
Amino Acid Decarboxylase ◽  
Corpora Cardiaca ◽  
Pericardial Cells ◽  
Semicarbazide Hydrochloride

1. Semicarbazide hydrochloride and isonicotinic acid hydrazide, which are both inhibitors of phosphopyridoxal-dependent systems, inhibit the increase in the rate of beating of hearts which is brought about by breis of corpora cardiaca. This inhibition is partially reversed by phosphopyridoxal. 2. Semicarbazide decreases the percentage of argentaffin-positive cells among pericardial cells exposed to breis of corpora cardiaca. 3. DOPA increases the rate of beating of the isolated heart. This increase is mediated by the pericardial cells and is inhibited by semicarbazide. The inhibition by semicarbazide is reversed by phosphopyridoxal. 4. It is suggested, as a working hypothesis, that the hormone from the corpus cardiacum stimulates the pericardial cells to produce an amine from an amino acid by the action of the appropriate amino acid decarboxylase. The hormone intervenes either by causing the cells to produce more of the amino acid, or by unmasking the amino acid which is pictured as being protected from the enzyme in the unstimulated cell.

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