Inhibition aminobutyric acid

Mode of Motion. The cyclodienes, like lindane and toxaphene, affect the nerve axon produciag hyperactivity, convulsions, prostration, and death. The biochemical lesion is the competitive inhibition of the y-aminobutyric acid (GABA) neurotransmitter binding site of the nerve axon. Spray workers with lengthy exposure to dieldrin have suffered from prolonged and repeated central nervous system disturbances produciag epileptiform coavulsioas. Similar disturbances occurred ia workers heavily exposed to chlordecoae. 

Another class of therapeutic agents is used for the treatment of certain genetic diseases or other enzymatic disorders caused by the dysfunction or absence of one particular enzyme. This often leads to an unwanted accumulation or imbalance of metaboUtes in the organism. Eor example, some anticonvulsive agents are inhibitors for y-aminobutyric acid aminotransferase [9037-67-6]. An imbalance of two neurotransmitters, glutamate and y-aminobutyric acid, is responsible for the symptoms. Inhibition of the enzyme leads to an increase of its substrate y-aminobutyric acid, decreasing the imbalance and subsequently relieving the symptoms of the disease. 

Tetanus is a disease caused by the release of neurotoxins from the anaerobic, spore-forming rod Clostridium tetani. The clostridial protein, tetanus toxin, possesses a protease activity which selectively degrades the pre-synaptic vesicle protein synaptobrevin, resulting in a block of glycine and y-aminobutyric acid (GABA) release from presynaptic terminals. Consistent with the loss of neurogenic motor inhibition, symptoms of tetanus include muscular rigidity and hyperreflexia. The clinical course is characterized by increased muscle tone and spasms, which first affect the masseter muscle and the muscles of the throat, neck and shoulders. Death occurs by respiratory failure or heart failure. 

Costa, L.G. 1985. Inhibition of gamma — [3H] aminobutyric acid uptake by organotin compounds in vitro. Toxicol. Appl. Pharmacol. 79 471-479. 

Treatment approaches include (1) reduction of blood ammonia concentrations by dietary restrictions, and drug therapy aimed at inhibiting ammonia production or enhancing its removal (lactulose and antibiotics) and (2) inhibition of y-aminobutyric acid-benzodiazepine receptors by flumazenil. 

The CNS also contains a descending system for control of pain transmission. This system originates in the brain and can inhibit synaptic pain transmission at the dorsal horn. Important neurotransmitters here include endogenous opioids, serotonin, norepinephrine, y-aminobutyric acid, and neurotensin. 

Larsson, O. M., Falch, E., Krogsgaard-Larsen, P, and Schousboe, A. (1988) Kinetic characterization of inhibition of y-aminobutyric acid uptake into cultured neurons and astrocytes by 4,4-diphenyl-3-butenyl derivatives of nipecotic acid and guvacine. J. Neurochem. 50, 818-823. 

Larsson, O. M., Griffiths, R., Allen, I. C., and Schousboe, A. (1986) Mutual inhibition kinetic analysis of gamma-aminobutyric acid, taurine and beta-alanine high-affinity transport into neurons, and astrocytes evidence for similarity between the taurine and beta-ala-nine carriers in both cell types. J. Neurochem. 47,426 132. 

Bloomquist JR, Adams PM, Soderiund DM. 1986. Inhibition of gamma-aminobutyric acid-stimulated chloride flux in mouse brain vesicles by polychlorocycloalkane and pyrethroid insecticides. Neurotoxicology 7(3) 11-20. 

Kardos J, Blandl T. (1994). Inhibition of a gamma aminobutyric acid A receptor by caffeine. Neuroreport. 5(10) 1249-52. 

Riedel E, Hansel R, Ehrke G. (1982). [Inhibition of gamma-aminobutyric acid catabolism by valerenic acid derivatives]. Planta Med. 46(4) 219-20. 

Hada J, Kaku T, Jiang MH, Morimoto K, Hayashi Y. 2003. Inhibition of high K -evoked gamma-aminobutyric acid release by sodium nitroprusside in rat hippocampus. Eur J Pharmacol 467(1-3) 119-123. 

Heptachlor epoxide is more toxic then heptachlor. The acute oral LD50 for heptachlor epoxide in rodents and rabbits ranged from 39 to 144mg/kg3 After dietary exposure of rats, heptachlor epoxide caused hepatic cell vacuolization at all dose levels (0.5-10 ppm for up to 108 weeks). Degeneration, hepatomegaly, and regeneration were also reported. Like heptachlor, the ability of heptachlor epoxide to induce lethality after acute exposure may involve its ability to interfere with nerve action or release of neurotransmitters and to inhibit the function of the receptor for y-aminobutyric acid. ... 

One proposed mechanism for toxaphene-induced neurotoxicity is that it acts as a noncompetitive y-aminobutyric acid (GABA) antagonist at the chloride channel in brain synaptosomes. Substances that bind to the GABA-regulated chloride channel induce convulsions by inhibiting chloride flux thus allowing brain cells to depolarize and fire spontaneously. ... 

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