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Cyclosporine
Cyclosporine or ciclosporin (INN) or cyclosporin (former BAN), is an immunosuppressant drug. It is used post-allogenic organ transplant to reduce the activity of the patient's immune system and so the risk of organ rejection. It has been studied in transplants of skin, heart, kidney, lung, pancreas, bone marrow and small intestine. Cyclosporine is a cyclic nonribosomal peptide of 11 amino acids produced by the ascomycete fungus Beauveria nive. Since 2002 a topical emulsion of cyclosporine for treating dry eye disease (keratoconjunctivitis sicca) has been aggressively marketed under the trade name Restasis®. Cyclosporine is also an antipsoriatic and an antirheumatic, although it is only used in severe cases. It has been investigated in connection with a great many diseases. It is often taken in conjunction with corticosteroids. The drug is sold by Novartis under the brand names Sandimmune® and Neoral®. Generic cyclosporine drugs have been produced by companies such as Sangstat, Abbott Laboratories and Gengraf. Annual sales of cyclosporine are around $1 billion. Cyclosporine is thought to bind to the cytosolic protein Cyclophylin (Immunophylin)of immunocompetent lymphocytes, especially T-lymphocytes. This complex of Cyclosporin and Cyclophylin inhibits Calcineurin, which under normal circumstances is responsible for activating the transcription of IL-2. It also inhibits lymphokine production and interleukin release and therefore leads to a reduced function of effector T-cells. It does not effect cytostatic activity. Treatment has a number of potentially serious side effects and has adverse interactions with a wide variety of other drugs and other materials including grapefruit, although there have been studies to improve the blood level of cyclosporine with grapefruit juice. Side effects can include gum hyperplasia, convulsions, peptic ulcers, pancreatitis, fever, vomiting, diarrhea, confusion, breathing difficulties, numbness and tingling, pruritus, high blood pressure, kidney and liver disfunction, potassium retention and possibly hyperkalemia, hepatotoxicity, nephrotoxicity, and obviously an increased vulnerability to opportunistic fungal and viral infections. Cyclosporine was discovered in 1970 in a Norwegian soil fungus by Jean F. Borel at Sandoz laboratories and it was approved for use in 1983. The chemical name of cyclosporine is [R-[R*,R*-(E)]]-cyclic(L-alanyl-D-alanyl-N-methyl-L-leucyl-N-methyl-L-leucyl-N-methyl-L-valyl-3-hydroxy-N,4-dimethyl-L-2-amino-6-octenoyl-L-α-amino-butyryl-N-methylglycyl-N-methyl-L-leucyl-L-valyl-N-methyl-L-leucyl) and the empirical formula is C62H111N11O12. Compare with tacrolimus. External linkPDF at Novartis (http://www.pharma.us.novartis.com/product/pi/pdf/sandimmune.pdf)
Categories: Immunosuppressive agents
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