      Document 0024
 DOCN  DRG0024
 UNIQUE IDENTIFIER        DRG-0223
 NAME OF SUBSTANCE        Mitoguazone dihydrochloride [Merck Index
                          1989]
 REGISTRY NUMBER          7059-23-6
 STANDARD CHEMICAL NAME   Hydrazinecarboximidamide,
                          2,2'-(1-methyl-1,2-ethanediylidene)bis-,
                          dihydrochloride [CHEMLINE]
 SYNONYMS                 MGBG [Int J Biochem Cell Biol 1995 Jan;27(1)]
 SYNONYMS                 Methyl-GAG [Merck Index 1989]
 SYNONYMS                 Methylglyoxal bis(guanylhydrazone)
                          dihydrochloride [CHEMID]
 SYNONYMS                 Methyl glyoxal bis(amidinohydrazone)
                          dihydrochloride [CHEMID]
 SYNONYMS                 Guanylhydrazone dihydrochloride [CHEMID]
 PROTOCOL ID NUMBERS      FDA 241A
 SECONDARY SOURCE ID      NSC-32946 [Merck Index 1989]
 PHARMACOLOGICAL ACTION   MODE OF ACTION: Inhibits biosynthesis of
                          polyamines, which play an important role in
                          regulation of cell proliferation,
                          differentiation, and functional stimulation
                          of terminally differentiated cells. MGBG
                          crosses the blood brain barrier and appears
                          to work in patients with inanition (a
                          condition characterized by marked weakness,
                          extreme weight loss, and decreased
                          metabolism). In vitro studies with HeLa cells
                          treated with MGBG showed a marked depression
                          in levels of the cellular polyamines
                          putrescine, spermidine, and spermine.  Other
                          studies indicate that MGBG diminishes the
                          respiratory burst activity of macrophages
                          induced by lipopolysaccharides and interferon
                          gamma; this inhibitory effect of MGBG was
                          concentration-dependent and could be reversed
                          by spermine, which is the final product of
                          polyamine biosynthesis. [Cancer Lett 1993 Aug
                          16;72(1-2); Ann Oncol 1994 Jul;5(6); J Leukoc
                          Biol 1992 Dec;52(6)]
 DISEASES STUDIED/TREATED AIDS-related non-Hodgkin's lymphoma [FDA
                          241A]
 CLASSIFICATION CODE      Antineoplastic [Merck Index 1989]
 OTHER MAJOR USES         Non-small cell lung cancer, Hodgkin's disease
                          [Invest New Drugs 1993 Feb;11(1); Ann Oncol
                          1994 Jul;5(6]
 ADVERSE EFFECTS          Adverse effects have included flushing,
                          tingling, euphoria, or somnolence during
                          infusion. Other adverse effects have included
                          mild nausea, vomiting, fatigue, and
                          neutropenia. [Proc Annu Meet Am Soc Clin
                          Oncol 13 1994 A11]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: Structural analog of
                          spermidine [Biochem Pharmacol 1993 Sep
                          14;46(6)]
 CHEMICAL/PHYSICAL DATA   MOLECULAR FORMULA: C5H14Cl2N8 [Merck Index
                          1989]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Intravenous. [FDA 241A]
 MANUFACTURERS            ILEX Oncology Inc
 REFERENCES               Shao D, Xiao L, Ha HC, Casero RA Jr.
                          Isolation of a polyamine transport deficient
                          cell line from the human non-small cell lung
                          carcinoma line NCI H157. J Cell Physiol 1996
                          Jan;166(1):43-8.
 REFERENCES               Ferme C, Bastion Y, Lepage E, Berger F, Brice
                          P, Morel P, Gabarre J, Nedellec G, Reman O,
                          Cheron N, et al. The MINE regimen as
                          intensive salvage chemotherapy for relapsed
                          and refractory Hodgkin's disease [see
                          comments]. Ann Oncol 1995 Jul;6(6):543-9.
 REFERENCES               Levine AM, Weiss GR, Tulpule A, Kaplan L,
                          Giles F, Luskey BD, Scadden DT, Pearce T,
                          Silverberg I, Busquets A, et al. Multicenter
                          phase II study of mitoguazone (MGBG) in
                          relapsed or refractory AIDS-lymphoma (Meeting
                          abstract). Proc Annu Meet Am Assoc Cancer
                          Res;14:A821 1995.
 REFERENCES               Von Hoff, DD. MGBG: teaching an old drug new
                          tricks. Ann Oncol. 1994 Jul;5(6):487-93.
 REFERENCES               Levine AM, Weiss G, Tulpule A, Espina B,
                          Anderson LJ, Boswell W, Esplin J, Von Hoff D.
                          MGBG: a highly active drug in relapsed or
                          refractory AIDS-lymphoma (Meeting abstract).
                          Proc Annu Meet Am Soc Clin Oncol; 13:All
                          1994.
 REFERENCES               Knight WA 3d, Fabian C, Costanzi JJ, Jones
                          SE, Coltrman CA Jr. Methyl-glyoxal bis guanyl
                          hydrazone (Methyl-GAG, MGBG) in lymphoma and
                          Hodgkin's disease. A Phase II trial of the
                          Southwest Oncology Group. Invest New Drugs.
                          1983;1(3):235-7.
 REFERENCES               Kelsen DP, Yagoda A, Warrell R, Chapman R,
                          Whittes R, Gralla RJ, Casper E, Young CW.
                          Phase II trials of methylglyoxal-bis
                          (guanylhydrazone). Am J Clin Oncol. 1982
                          Apr;5(2):221-5.
 ENTRY MONTH              9505
 LAST REVISION DATE       960424
 

SOURCE: National Library of Medicine, Bethesda, MD.  Distributed by AEGIS.
