Inhibitor folate

Folate inhibitors, bacterial resistance mechanisms, 3 32t Folate metabolism, 23 502 Folcysteine, 13 431, 52 Folded guide microwave applicator, 16 522 Folding-carton inks, 14 321 Folding carton packaging, converting, 25 21-22... 

Drugs that may affect lamotrigine include acetaminophen, carbamazepine, folate inhibitors, oral contraceptives, phenobarbital, phenytoin, primidone, rifamycins, succinimides, and valproic acid. 

Increased effect with folate inhibitors, valproic acid... 

The mechanism of resistance to the folate inhibitor combination has been shown to be associated with point mutations in both DHFR and the dihydropteroate synthase enzymes (35). 

Inhibitors of Folate Metabolism Provide Cancer Chemotherapy Antibacterial Antimalarial Drugs... 

Among these drugs, the dihydrofolate reductase (DHFR) inhibitors are used clinically with a certain amount of success. They belong to two major classes the classical antifolates which feature a polar amino-acid side chain terminus and those containing nonpolar side chains, called lipophilic or nonclassical anti-folates. 

Freer, Calculation of solvation and binding free energy differences for folate-based inhibitors of the enzyme thymidylate synthase, J. Am. Chem. Soc. 114 10117 (1992). 

The enzyme mediating remethylation, 5-methyltetrahy-drofolate-betaine methyltransferase (Fig. 40-4 reaction 4), utilizes methylcobalamin as a cofactor. The kinetics of the reaction favor remethylation. Faulty remethylation can occur secondary to (1) dietary factors, e.g. vitamin B12 deficiency (2) a congenital absence of the apoenzyme (3) a congenital inability to convert folate or B12 to the methylated, metabolically active form (see below) or (4) the presence of a metabolic inhibitor, e.g. an antifolate agent that is used in an antineoplastic regimen. 

Inhibit Enzymes Many drugs are competitive inhibitors of key enzymes in pathways. The statin drugs (lovastatin, simvastatin), used to control blood cholesterol levels, competitively inhibit 3-hvdroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase in cholesterol biosynthesis. Methotrexate, an antineoplastic drug, competitively inhibits dihydrofolate reductase, depriving the cell of active folate needed for purine and deoxythymidine synthesis, thus interfering with DNA replication during S phase. 

Pharmacology Trimetrexate, a 2.4-diaminoquinazoline, nonclassical folate antagonist, is a synthetic inhibitor of the enzyme dihydrofolate reductase. The end result is disruption of DNA, RNA, and protein synthesis, with consequent cell death. Pharmacokinetics Clearance was 38 15 ml /min/m and volume of distribution at steady state (Vdgs) was 20 8 L/m. The plasma concentration time profile declined... 

The DNA-mediated effects of fluropyrimidines can be modulated by a number of agents, such as leucovorin (LV), levamisole, and interferon-alpha (IFN-alpha). LV prolongs TS inhibition by increasing the availability of the reduced folate cofactor necessary for formation of the inactive TS-FdUMP complex (21) (Fig. 4). Studies show alpha-interferon can potentiate 5-FU-mediated cyotoxicity, but the mechanisms are not yet defined (22,23). Another approach to modulate the activity of fluoropyrimidines is the use of the nucleoside transport inhibitor dipyridamole. Dipyridamole probably permits... 

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