咪唑啉
霉酚酸酯
霉酚酸
医学
化学
药理学
IMP脱氢酶
硫唑嘌呤
类风湿性关节炎
白色念珠菌
移植
药代动力学
前药
免疫抑制
不利影响
他克莫司
狼疮性肾炎
免疫学
微生物学
内科学
生物
疾病
标识
DOI:10.2174/092986730607220401123549
摘要
Both mizoribine (MZR) and mycophenolate mofetil (MMF) are immunosuppressive agents that inhibit the proliferation of lymphocytes selectively, via inhibition of IMPDH. MZR is a nucleoside of the imidazole class, isolated from the culture medium of the mold Eupenicillium brefeldianum M-2166. Although this compound has been found to have weak antimicrobial activity against Candida albicans, it has proved ineffective against experimental candidiasis. Unlike azathioprine , this compound is not taken up by nucleic acids in the cell. Instead, after phosphorylation MZR-5'-monophosphate inhibits GMP synthesis by the antagonistic blocking of IMPDH (Ki = 10 - 8 M) and GMP- synthetase (Ki =10 -5 M). The drug has been found to inhibit both humoral and cellular immunity, and on this basis it was developed in Japan as an immunosuppressant. MZR has been shown in animal experiments to lack oncogenicity, and has been shown clinically to be associated with a low incidence of severe adverse reactions. MZR has been registered in Japan for the prevention of rejection in renal transplantation, and for the treatment of lupus nephritis, rheumatoid arthritis and the nephrotic syndrome. MMF is the morpholinoethyl ester prodrug of mycophenolic acid (MPA), which was first isolated in 1896 from the culture media of several Penicillium species. MPA has been evaluated for its unique properties as an anticancer, antiviral, antifungal and antibacterial agent , as well as for its therapeutic use in psoriasis and rheumatoid arthritis. MMF was designed to enhance the oral bioavailability of the parent compound. After beneficial effects were observed in animals , the clinical efficacy of MMF as an immunosuppressant in renal transplantation was studied in the United States. In 1995 the US Food and Drug Administration (FDA) approved the use of MMF for the prevention of rejection in renal transplantation , the drug also available on a number of European markets.
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