      Document 0233
 DOCN  DRG0233
 UNIQUE IDENTIFIER        DRG-0014
 NAME OF SUBSTANCE        Dextran sulfate [Merck Index 1989]
 REGISTRY NUMBER          9042-14-2
 RELATED REGISTRY NUMBER  50935-34-7 [CHEMLINE]
 RELATED REGISTRY NUMBER  73075-68-0 (dextran sulfate) [CHEMLINE]
 RELATED REGISTRY NUMBER  9011-18-1 (dextran sulfate sodium) [CHEMLINE]
 RELATED REGISTRY NUMBER  9057-27-6 (dextran sulfate) [CHEMLINE]
 RELATED REGISTRY NUMBER  9063-02-9 (dextran sulfate) [CHEMLINE]
 STANDARD CHEMICAL NAME   Dextran hydrogen sulfate [CHEMLINE]
 SYNONYMS                 Dextran sulfate sodium [Merck Index 1989]
 SYNONYMS                 Dextran sulfuric acid ester sodium salt
                          [Merck Index 1989]
 SYNONYMS                 Asuro [Merck Index 1989]
 SYNONYMS                 Colyonal [Merck Index 1989]
 SYNONYMS                 Dexulate [Merck Index 1989]
 SYNONYMS                 Dextrarine [Merck Index 1989]
 SYNONYMS                 MDS [Merck Index 1989]
 SYNONYMS                 PF51 [CHEMLINE]
 PROTOCOL ID NUMBERS      NIAID ACTG 060
 PROTOCOL ID NUMBERS      NIAID ACTG 078
 PROTOCOL ID NUMBERS      NIAID ACTG 105
 SECONDARY SOURCE ID      UA001 [NIAID ACTG 060]
 PHARMACOLOGICAL ACTION   MODE OF ACTION: The main mechanism of HIV
                          inhibition by most sulfated polyanions
                          involves the sulfated polyanion binding to a
                          site close to the gp120 binding region of
                          CD4, thereby disrupting gp120-CD4
                          interaction.  The higher the MW of dextran
                          sulfate the more potent the anti-HIV effect.
                          Dextran sulfate does not directly block
                          gp120-CD4 interactions. The rapid decrease in
                          the amount of gp120 on the surface of the
                          infected cells suggests that the effects of
                          dextran sulfate include the disruption of
                          gp120 cell surface expression resulting in
                          inhibition of syncytia formation. Dextran
                          sulfate blocks the cell fusion and protects
                          the cell from death on HIV-1 env gene
                          expressing CD4+ T and monocytoid cells. [Int
                          Conf AIDS 1990 Jun 20-23;(1); abstract no.
                          Th.A. 238] [Int Conf AIDS 1989 Jun 4-9;5;
                          abstract no. C.635] [Int Conf AIDS 1994 Aug
                          7-12;10(1); abstract no. PA0038]
 DISEASES STUDIED/TREATED Treatment of HIV in AIDS patients [NIAID ACTG
                          060] [Int Conf AIDS 1989 Jun 4-9;5; abstract
                          no. M.V.P. 75]
 CLASSIFICATION CODE      Antiretroviral [Drug Evaluations Annual 1995]
 OTHER MAJOR USES         Anticoagulant and antiarteriosclerotic agent
                          [Merck Index 1989]
 SUBSTANCE INTERACTIONS   In combination with dideoxynucleosides, the
                          high molecular weight range of dextran
                          sulfate (500,000 Da) resulted in an
                          antagonistic response directed against the
                          two clinical isolates of HIV (HIV TM and SP)
                          when the antiviral concentrations of dextran
                          sulfate were in the ineffective range.
                          Additive or synergistic effects were seen
                          with the other three HIV isolates and all 5
                          HIV isolates when the low molecular weight
                          range of dextran sulfate was used. Dextran
                          sulfate application did neither enhance
                          adverse drug effects of zidovudine nor induce
                          severe disorders of blood coagulation. The
                          beneficial effect of castanospermine (CSP)
                          and dextran sulfate (DS) on CD4+ T cells is
                          counteracted by the observation that both
                          drugs also permit the growth of in vivo
                          HIV-infected CD4+ T cells. The expansion of
                          the population of HIV-infected cells may
                          cause an undesirable increase in the viral
                          load in the host. Thus both drugs may have to
                          be used in combination with drugs that
                          prevent virus replication. [Biochem Soc Trans
                          1992 May;20(2):163S] [Int Conf AIDS 1989 Jun
                          4-9;5; abstract no. W.B.P. 324] [Int Conf
                          AIDS 1989 Jun 4-9;5; abstract no. Th.B.O. 48]
 ADVERSE EFFECTS          May cause diarrhea or abdominal bloating,
                          neutropenia, thrombocytopenia, elevation in
                          hepatic transaminases, dysphoric mental
                          hyperactivity, and insomnia. Intravenous
                          infusion may cause nausea, anorexia,
                          arthralgias, skin eruptions, transient
                          alopecia, and headache. [NIAID ACTG 060]
                          [ACTG 078]
 CONTRAINDICATIONS        Should not be used by pregnant or nursing
                          women. [ACTG 060]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: Sulfated polysaccharide
                          containing up to three sulfate groups per
                          glucose unit [Merck Index 1989] [Int Conf
                          AIDS 1990 Jun 20-23;6(1); abstract no. Th.A.
                          238]
 CHEMICAL/PHYSICAL DATA   MOLECULAR FORMULA: Sulfate of poly(D-glucose)
                          [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   MOLECULAR WEIGHT: 4,000-500,000 [Merck Index
                          1989]
 CHEMICAL/PHYSICAL DATA   PERCENT ELEMENTAL COMPOSITION: 17-20 percent,
                          sulfur content [NIAID ACTG 060]
 CHEMICAL/PHYSICAL DATA   SOLUBILITY: Freely soluble in water [Merck
                          Index 1989]
 CHEMICAL/PHYSICAL DATA   PHYSICAL DESCRIPTION: White powder [Merck
                          Index 1989]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: Capsules(300 mg). [NIAID ACTG
                          060]
 SUBSTANCE DELIVERY DATA  Sterile solution (225 mg/20 ml normal
                          saline). [NIAID ACTG 078]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Oral; intravenous infusion.
                          [NIAID ACTG 078]
 MANUFACTURERS            Ueno Fine Chemicals
 REFERENCES               Neyts J, De Clercq E. Effect of polyanionic
                          compounds on intracutaneous and intravaginal
                          herpes virus infection in mice: impact on the
                          search for vaginal microbicides with anti-HIV
                          activity. J Acquir Immune Defic Syndr Hum
                          Retrovirol. 1995 Sep 1;10(1):8-12.
 REFERENCES               Gordon LM, Waring AJ, Curtain CC, Kirkpatrick
                          A, Leung C, Faull K, Mobley PW. Antivirals
                          that target the amino-terminal domain of HIV
                          type 1 glycoprotein 41. AIDS Res Hum
                          Retroviruses. 1995 Jun;11(6):677-86.
 REFERENCES               Okada T, Gurney ME. Single basic amino acid
                          substitutions at position 302 or 320 in the
                          V3 domain of HIV type 1 are not sufficient to
                          alter the antiviral activity of dextran
                          sulfate and heparin. AIDS Res Hum
                          Retroviruses. 1995 May;11(5):571-5.
 REFERENCES               Okada T, Patterson BK, Gurney ME. Inhibition
                          of anti-V3 domain antibody binding to human
                          immunodeficiency virus type-1-infected cells
                          by sulfated polysaccharides. Biochem Biophys
                          Res Commun. 1995 Apr 26;209(3):850-8.
 REFERENCES               Meylan PR, Kornbluth RS, Zbinden I, Richman
                          DD. Influence of host cell type and V3 loop
                          of the surface glycoprotein on susceptibility
                          of human immunodeficiency virus type 1 to
                          polyanion compounds. Antimicrob Agents
                          Chemother. 1994 Dec;38(12):2910-6.
 REFERENCES               Bergamini A, Perno CF, Dini L, Capozzi M,
                          Pesce CD, Ventura L, Cappannoli L, Falasca L,
                          Milanese G, Calio R, et al. Macrophage
                          colony-stimulating factor enhances the
                          susceptibility of macrophages to infection by
                          human immunodeficiency virus and reduces the
                          activity of compounds that inhibit virus
                          binding. Blood. 1994 Nov 15;84(10):3405-12.
 REFERENCES               Lynch G, Low L, Li S, Sloane A, Adams S,
                          Parish C, Kemp B, Cunningham AL. Sulfated
                          polyanions prevent HIV infection of
                          lymphocytes by disruption of the CD4-gp120
                          interaction, but do not inhibit monocyte
                          infection. J Leukoc Biol. 1994
                          Sep;56(3):266-72.
 REFERENCES               Ida H, Kurata A, Eguchi K, Yamashita I,
                          Nakashima M, Sakai M, Kawabe Y, Nakamura T,
                          Nagataki S. Mechanism of inhibitory effect of
                          dextran sulfate and heparin on human T-cell
                          lymphotropic virus type 1 (HTLV-1)-induced
                          syncytium formation in vitro: role of
                          cell-to-cell contact. Antiviral Res. 1994
                          Feb;23(2):143-59.
 REFERENCES               Lopalco L, Ciccomascolo F, Lanza P, Zoppetti
                          G, Caramazza I, Leoni F, Beretta A, Siccardi
                          AG. Anti-HIV type 1 properties of chemically
                          modified heparins with diminished
                          anticoagulant activity. AIDS Res Hum
                          Retroviruses. 1994 Jul;10(7):787-93.
 REFERENCES               Flexner C, Barditch-Crovo PA, Kornhauser DM,
                          Farzadegan H, Nerhood LJ, Chaisson RE, Bell
                          KM, Lorentsen KJ, Hendrix CW, Petty BG, et
                          al. Pharmacokinetics, toxicity, and activity
                          of intravenous dextran sulfate in human
                          immunodeficiency virus infection. Antimicrob
                          Agents Chemother. 1991 Dec;35(12):2544-50.
 ENTRY MONTH              8906
 LAST REVISION DATE       960501
 

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