Ciclosporin

• Cyclosporin A
• Cyclo - (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 -La -amino- butyryl -N- methylglycyl -N-methyl -L-leucyl -L-valyl -N-methyl -L-leucyl )

• L04AD01
• S01XA18

Immunosuppressants

Calcineurin inhibitor

148-151 ° C

Soluble in methanol

Risk

Template: Infobox chemical / molecular formula search available

Ciclosporin ( INN), cyclosporin A, a drug from the group of immunosuppressants, which is isolated from the Norwegian sac fungi Tolypocladium inflatum (W. Gams ) and Cylindrocarpon lucidum ( Booth). The substance is a cyclic peptide consisting of eleven amino acids. Cyclosporine suppresses the immune system by indirectly inhibiting the enzyme calcineurin, and is mainly used in transplantation to prevent organ rejection. Cyclosporine has a narrow therapeutic range, so that on internal use regular blood level controls ( therapeutic drug monitoring) is required. In a transplant cyclosporine was used for the first time in 1978. The use revolutionized this part of the field of medicine, the survival time of the patients increased significantly.

As an explorer Jean -François Borel and Hartmann Stähelin apply at Sandoz in Basel in the early 1970s.

Pharmacology

Mechanism of action

Cyclosporin binds to the immunophilin, cyclophilin A ( a prolyl -cis -trans- isomerase ) and this complex binds to calcineurin ( a calcium / calmodulin-dependent phosphatase). Thus, in the cytoplasm, the binding of NF -AT (short for nuclear factor activating T -Cell ), a gene - regulating protein blocked. In activated T cells, calcineurin is responsible for the dephosphorylation of NF-AT. NF-AT can then be translocated to the nucleus and there to enable the reading of a number of genes, cytokines and cell surface receptors ( inter alia, interleukin-2 and γ - interferon). By calcineurin inhibition that is, the distribution of immunostimulating substances and thus the activation and proliferation of lymphocytes is inhibited. In this way it acts as an immunosuppressant.

Areas of application

Cyclosporine -containing drugs are used in ulcerative colitis, Crohn's disease, glomerulonephritis, skin disorders (particularly heavy, treatment-resistant forms of atopic dermatitis, and psoriasis ), and chronic inflammatory conditions of the conjunctiva and the cornea ( cyclosporin A eye drops according to NRF 15.21 ). It is also used to treat alopecia areata, in combination with methylprednisolone with very high treatment success. In veterinary medicine, it is occasionally used in the atopic dermatitis of the dog and the cat with chronic stomatitis.

In the treatment of tumors, it prevents, together with the transport of verapamil certain tumor chemotherapeutic agents out of the cell by the P- glycoprotein multidrug resistance 170.

Moreover, it is administered after transplantation to avoid graft rejection.

Side effects

Possible side effects include damage to the kidneys, the liver and the gastrointestinal tract. In addition, cyclosporine can lead to gum overgrowth, hirsutism, edema and high blood pressure.

Regular intake of high doses of cyclosporine, as is the case in transplant patients, lead to a weakening of the immune system. Thereby, the risk of cancer increases significantly. Relative to the normal population, the cancer probability is higher by a factor of three to five. In addition, there - also by the immunosuppression caused - an increased risk of infections. The blood fat levels may be elevated. Strong sunlight should be avoided if ingested. Thus a simultaneous light therapy closes when intake due to a skin disease (UV ) radiation from. Cyclosporine can lead to fibroadenomas.

Trade names

Monopreparations

Cicloral (D, A), Ciclosol (CH), Immunosporin (D), Neoimmun (A), Sandimmune Optoral (D, A, CH ), various generics (D) Special Feature: Restasis (USA; 0.05% aqueous suspension of cyclosporin A solution for the treatment of keratoconjunctivitis sicca, approved in the U.S. only )