Antineoplastic agents methotrexate

F. Palmisano, T.R.I. Cataldi and P.G. Zambonin, Determination of the antineoplastic agent methotrexate in body fluids by high-performance liquid chromatography with electrochemical detection, J. Chromatogr., 1985, 344, 249-258. 

Trimetrexate (88) Is an antineoplastic agent related to the well-established folic acid antimeta-bolite methotrexate. It can be synthesized by selective diazotization of the most basic amino group of 2,4,6-triamino-5-methylquinazoline (85) followed by a Sandmeyer displacement with CuCN to give nitrile 86. Careful reduction asing Raney nickel produces the aminomethyl intermediate 87 or, if the reaction is carried out in the presence of 3,4,5-triniethoxyaniline, trimetrexate (88) [24]. One presumes that that outcome is a consequence of amine exchange at the partially reduced imine stage and further reduction. 

Other classes of proteins that have been clearly identified as drug receptors include enzymes, which may be inhibited (or, less commonly, activated) by binding a drug (eg, dihydrofolate reductase, the receptor for the antineoplastic drug methotrexate) transport proteins (eg, Na+/K+ ATPase, the membrane receptor for cardioactive digitalis glycosides) and structural pro-teins (eg, tubulin, the receptor for colchicine, an anti-inflammatory agent). 

Dactinomycin is an antineoplastic agent that is the principal component of the mixture of actinomycins produced by Streptomyces parvullus. It inhibits messenger RNA synthesis. Dactinomycin (0.5 mg/day IV for 5 days), in combination with vincristine, radiotherapy, and surgery, is used in Wilms tumor in conjunction with vincristine, cyclophosphamide, and doxorubicin, it is used in choriocarcinoma in combination with methotrexate, it is used in testicular carcinoma and in combination with cyclophosphamide and radiotherapy, it is used in Ewing s sarcoma. Dactinomycin inhibits messenger RNA synthesis by anchoring to a purine-pyrimidine (DNA) base pair by intercalation (see Figure 15). The toxicity of dactinomycin increases when combined with radiation therapy. 

Aside from its antineoplastic activity, methotrexate also has been used with benefit in the therapy of psoriasis. Additionally, it inhibits cell-mediated immune reactions and is employed as an immunosuppressive agent to suppress graft-versus-host disease in allogenic bone marrow and organ... 

Pteridines are also used as pharmaceuticals. Triamterene 15 is a diuretic that promotes excretion of Na" and retains K+. The folic acid antagonist methotrexate 16 (amethopterin) is of considerable importance as an antineoplastic agent in cancer chemotherapy. 

The client is prescribed methotrexate (Rheumatrex), an antineoplastic agent, for psoriasis. Which data should the nurse monitor ... 

Methotrexate Magnetic nanoparticles— poly(ethylene glycol, magnetic nanoparticles-3-aminopropyl) trimethoxysilane Antineoplastic agent... 

Inhibitors of bacterial folate synthesis are considered here. Folate antagonists used as antineoplastic agents, i.e. methotrexate and lometrexol, are discussed in Section 3. 

Exp. reprod. and teratogenic effects (large dose), human adverse systemic effects (large dose), exp. antineoplastic agent (and in co-administration with methotrexate, see Methotrexate). LD50 (mus, ipr) 2512 mg/kg. XP2071000 3 -Phosphate See Thymidine 3 -phos-phate, T-107... 

Trade names Cisplatyl Plasticin Platiblastin Platinex Platinol (Bristol-Myers Squibb) Platinol-AQ Platistil Indications Carcinomas, lymphomas Category Alkylating agent Antineoplastic Half-life a phase 25-49 minutes (3 phase 58-73 hours Clinically important, potentially hazardous interactions with aldesleukin, atenolol, chlorothiazide, methotrexate, selenium, torsemide, zinc... 

Antiviral agents acyclovir, amantadine, azidofhymidine Diuretics furosemide, hydrochlorothiazide, efhacrynic acid ACE inhibitors captopril, enalapril, ramipril, delapril, quinapril Antineoplastics methotrexate, azathioprine, doxorubicin, 5-fluouracil Antiepileptics valproic acid (from Ref. [95])... 

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