Reference

New immunosuppressive drugs in organ transplantation

New immunosuppressive drugs in organ transplantation. Hughes, Stephen E.; Gruber, Scott A. (Section of Transplantation, Department of Surgery, Albany Medical College, Albany, NY, USA). Journal of Clinical Pharmacology, 36(12), 1081-1092 (English) 1996 Lippincott-Raven. CODEN: JCPCBR. ISSN: 0091-2700. DOCUMENT TYPE: Journal; General Review CA Section: 1 (Pharmacology) A review with 140 refs. An examn. of the mechanisms by which four new immunosuppressive drugs - rapamycin, mizoribine, mycophenolate mofetil, and 15-deoxyspergualin - exert their effects reveals three major categories. Rapamycin binds to an intracellular immunophilin. The resulting drug-immunophilin complex inhibits the action of cytokines, thus blocking the activation and proliferation of T cells. Mizoribine and mycophenolate mofetil are antimetabolites that inhibit a key enzyme in the de novo purine biosynthetic pathway. As a result, the proliferation of T cells and B cells is inhibited selectively compared with that of nonlymphoid cells because the salvage pathway is unavailable to lymphocytes. Finally, 15-deoxyspergualin has a unique mechanism of action, which includes suppressive effects on macrophage function, the induction of cytolytic T cells, B-cell reactivity, and antibody responses. The demonstrated synergism among certain immunosuppressants allows redn. in the dose of each agent to minimize the individual toxicities. As more of these new agents become available, it is likely that azathioprine will be replaced, and it may be possible to eliminate the need for long-term maintenance steroid therapy.

Rapamycin analogs as immunosuppressants and antifungals

Rapamycin analogs as immunosuppressants and antifungals. Hughes, Philip F.; Musser, John H. (American Home Products Corp., USA). U.S. US 5138051 A 11 Aug 1992, 4 pp. (United States of America). CODEN: USXXAM. CLASS: ICM: C07D491-06. NCL: 540456000. APPLICATION: US 91-741714 7 Aug 1991. DOCUMENT TYPE: Patent CA Section: 1 (Pharmacology) Redn. of the C-33 ketone (I) of rapamycin gives 33-deoxo-33(R)-hydroxyrapamycin (II) and thus prevents cleavage of the C31-C32 bond due to base degrdn. I was reduced by Na triacetoxyborohydride to obtain II. II had immunosuppressant, antifungal, and antiinflammatory activities.