Decarboxylase inhibition

Persson, S.-A. (1977) The effect of LSD and 2-bromo LSD on the striatal DOPA accumulation after decarboxylase inhibition in rats. Eur. J. Pharmacol., 43 73-83. 

The first syntheses of a-allenic a-amino acids [131,133] took advantage of Steg-lich s [134] protocol for the oxazole-Claisen rearrangement of unsaturated N-ben-zoylamino acid esters (Scheme 18.46). Thus, treatment of the propargylic ester 143 with triphenylphosphine and tetrachlormethane furnished the allenic oxazolone 144, which was converted into the amino acid derivative 145 by methanolysis. Stepwise deprotection finally led to the allenic DOPA analog 146, which shows a much higher decarboxylase-inhibiting activity than a-vinyl- and a-ethynyl-DOPA [133],... 

Diaz-Munoz M, Tapia R. 1988. Glutamate decarboxylase inhibition and vitamin Be metabolism in brain of cirrhotic rats chronically treated with carbon tetrachloride. J Neurosci Res 20 276- 382. 

Catechol O-methyltransferase inhibition represents therefore a valuable adjuvant to the L-DOPA decarboxylase inhibition. Unfortunately, tolcapone exhibited... 

Robert F, Lambassenas L, Ortemann C, Pujol JF, Renaud B (1993) Microdialysis monitoring of 3,4-dihydroxyphenylalanine accumulation after decarboxylase inhibition—A means of estimate in vivo changes in tyrosine hydroxylase activity of the rat locus ceruleus. J Neurochem 60 721-729. 

This has been achieved for the production of (146) in D. sphaerica by means of histidine decarboxylase inhibitors. Both a-methylhistidine and a-hydrazinohistidine (inhibitors for mammalian specific histidine decarboxylase) inhibited formation of histamine with the result that more (146) was synthesized at the expense of (144) (based on the radioactivity of the products after feeding [ H]histidine, [ C]isovaleric acid and inactive animomethylimidazole [145]). a-Methyldopa, an inhibitor of mammalian non-specific decarboxylase, was without effect on the proportions of the products formed. 

Cacabelos. R. et al. (1991) Histidine decarboxylase inhibition induced by a-fluoromethylhistidine provokes learning-related l pokinetic activity. Agents Actions, 33.131-134. 

Catechol 0-methyltransferase inhibition represents therefore a valuable adjuvant to the 1-DOPA decarboxylase inhibition. Unfortunately, toicapone exhibited severe liver damages and had to be removed from the market. The corresponding vinyiogue entacapone is devoided of these side effects. ... 

L-Dopa elimination is primarily by decarboxylation to dopamine. Additional pathways are by 3-O-methylation and transamination. With adequate decarboxylase inhibition, increased amounts of L-dopa are metabolized by the other pathways. The elimination half-life of L-dopa is about 1 hour, and this is extended to about U/2 hours with the addition of carbidopa. 30MD has a half-life of about 15 hours and accumulates with chronic dosing. 

Wu,F., Grossenbacher, D., and Gehring, H. (2007) New transition state-based inhibitor for human ornithine decarboxylase inhibits growth of tumor cells. Mol. Cancer Ther. 6, 1831-1839. 

NO has a cytostatic effect by inhibiting ATP synthesis [99] via Kreb s cycle (aconitase inhibition, [100]), glycolysis (GADPH inhibition) and mitochondrial respiration (NAD ubiquinone oxydoreductase and succinate ubiquinone oxydoreductase inhibitions, [101]). Another pathway is the ornithine decarboxylase inhibition. This enzyme is implicated in polyamine production necessary to cell proliferation and its activity is inhibited by NO in human colon cancer cells HT-29 and Caco-2 [102]. Furthermore NO directly inactivates ribonucleotide reductase [103] of TA3 cancer cells (murine breast cancer cells) [104]. This enzyme controlling DNA synthesis catalyses desoxyribonucleotides synthesis, and its inhibition blocks cells in S phase. This inhibition is rapid and reversible in K562 and TA3 cells [105]. 

Levine RS. Effect of histidine decarboxylase inhibition on gastric acid secretion in the rat. Fed Proc 24 1331-1333, 1965. 

Oates, J. A., Gillespie, L., Udenfriend, S. and Sjoerdsma, A., Decarboxylase inhibition and blood pressure reduction by a-methyl-3,4-dihydroxy-DL-phenylalanine, Science 131, 1890 (1960). 

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