Amino Acid Antagonists

The amino acid antagonists broadly act as a glutamine antagonists in the synthesis of formylglycinamidine ribotide from glutamine and formylglycinamide ribotide. 

Azaserine inhibits the growth of sarcoma 180 and several leukemias. In clinical trials, although there was improvement in some cases of Hodgkin s disease, acute leukemia in children and chronic lymphocytic leukemia, the results in general were not very encouraging. 

The drug is believed to be a glutamine antagonist that specifically inhiits purine biosynthesis and thus may exert antitumour activity. 

The recognitiion of antibiotics as an important class of antineoplastic agents is quite recent. Consequently, the production of antineoplastic agents through proper strain selection and controlled microbial fermentation conditions may ultimately optimize the formation of a particular component in an antibiotic mixture. 

A few important members of this category are described below, namely Dactinomycine Q Daunorubicin  

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Berry, S.C. Dawkins, S.L. and Lodge, D. Comparison of o-- and K -Opiate receptor ligands as excitatory amino acid antagonists. r J. Pharmacol 83 179-185, 1984b. 

Spinella M, Bodnar RJ. (1996). Excitatory amino acid antagonists in the rostro-ventral medulla inhibit mesencephalic morphine analgesia in rats. Pain. 64 545-52. 

Sveinbjornsdottir S, Sander JWAS, Upton D,etal(1993) The excitatory amino acid antagonist d-CPP-ene (sdz eaa-494) in patients with epilepsy. Epilepsy Res 16 165-174 Takano T, Lin JH, Arcnino G, et al (2001) Glntamate release promotes growth of malignant gliomas. Nat Med 7 1010-1015... 

Muir, K. W. and Lees, K. R. Clinical experience with excitatory amino acid antagonist drugs, Stroke 1995, 26, 503-513. 

Soja PJ, Finch DM, Chase MH (1987) Effect of inhibitory amino acid antagonists on masseteric reflex suppression during active sleep. Exp Neurol 96 178-193... 

Kawamata T., Katayama Y., Hovda D. A., Yoshino A., and Becker D. P. (1992) Administration of excitatory amino acid antagonists via microdialysis attenuates the increase in glucose utilization seen following concussive brain injury. J. Cereb. Blood Flow Metab. 12,12-24. 

Yamamoto T, Yaksh TL (1992) Spinal pharmacology of thermal hyperesthesia induced by constriction injury of sciatic nerve. Excitatory amino acid antagonists. Pain 49 121-128 Yamamoto Y, Ono H, Ueda A, Shimamura M, Nishimura K, Hazato T (2002b) Spinorphin as an endogenous inhibitor of enkephahn-degrading enzymes roles in pain and inflammation. Curr Protein Pept Sci 3 587-599... 

Rogawski, M.A. (1993) Therapeutic potential of excitatory amino acid antagonists Channel blockers and 2.3-ben xliaKpine. Trends Pharmacol. ScL. 14.325-331. 

Meldrum, B. S. (1991) Excitatory Amino Acid Antagonists, Blackwell, Oxford. 

Krogsgaard-Larsen, P, Ferkany, J. W., Nielsen, E. O., Madsen, U., Ebert, B., Johansen, J. S., Diemer, S. H., Bruhn, T, Beattie, D. T, Curtis, D. R. Novel class of amino acid antagonists at non-N-methyl-D-aspartic acid excitatory amino acid receptors. Synthesis, in vitro and in vivo pharmacology, and neuroprotection. J. Med. Chem. 1991,54,123-130. 

Graham WC, Robertson RG, Sambrook MA et al (1990) Injection of excitatory amino acid antagonists into the medial pallidal segment of a l-methyl-4-phenyl-1,2,3,6-tetrahydro-pyridine (MPTP) treated primate reverses motor symptoms of parkinsonism. Life Sci 47 PL91-PL97... 

Marek, P., Beneliyahu, S., Gold, M., Liebeskind, J.C., 1991. Excitatory amino acid antagonist (kynurenic acid and MK-801) attenuate the development of morphine tolerance in the rat. Brain Res. 547, 77-81. 

McCullogh, J., 1992. Excitatory amino acid antagonists and their potential for the treatment of ischemic brain damage in man. Br. J. Clin. Pharmacol. 34, 106-114. 

The above facts strongly support the unusual role of N-hydroxy-amino acids as amino acid antagonists. Powers stated that the methyl ester of chloroacetyl-N-hydroxyleucine (50) 108) and the formyl-N-hydroxyleucyl-alanyl-glycine amide (51) 109) are the first specific non-reversible termolysine inhibitors. They act through coordination of the zinc atom of this metalloprotein, as has been determined by X-ray crystallography 110). Compound (51) is also an inhibitor of elastase 111). 

White, W. F., Nadler, J. V., and Cotman, C. W., 1979, The effect of amino acid antagonists on synaptic transmission in the hippocampal formation in vitro, Brain Res. 164 177-194. 

De Sarro G, Ammendola D, Nava F, De Sarro A. Effects of some excitatory amino acid antagonists on imipenem-induced seizures in DBA/2 mice. Brain Res 1995 671 (1) 131 0. 

L-689,560 is an excitatory amino acid antagonist. It binds to but does not activate excitatory amino acid receptors, thereby blocking the actions of agonists. The drug is a selective antagonist for the glycine site on the A7-methyl-D-aspartate receptor. ... 

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