      Document 0134
 DOCN  DRG0134
 UNIQUE IDENTIFIER        DRG-0113
 NAME OF SUBSTANCE        Hypericin [AmFAR Tx Dir 1995;7(4)]
 REGISTRY NUMBER          548-04-9
 STANDARD CHEMICAL NAME   1,3,4,6,8,13-Hexahydroxy-10,11-dimethylphenan-
                          thro (1,10,9,8,-opqra)perylene-7,14-dione
                          [Merck Index 1989]
 SYNONYMS                 Hypericum red [Merck Index 1989]
 SYNONYMS                 Cyclo-Werrol [Merck Index 1989]
 SYNONYMS                 Cyclosan [Merck Index 1989]
 SYNONYMS                 Vimrxyn [Facts and Comparisons 1995]
 PROTOCOL ID NUMBERS      NIAID ACTG 150
 PROTOCOL ID NUMBERS      NIAID ACTG 258
 SECONDARY SOURCE ID      DRG
 PHARMACOLOGICAL ACTION   MODE OF ACTION: In vitro, hypericin inhibits
                          the assembly and budding of virions from
                          infected cells, possibly by direct
                          inactivation of virions or by interfering
                          with shedding of assembled virus particles at
                          the cell membrane. Hypericin and
                          pseudohypericin inhibit protein kinase C
                          (PKC) in vitro. The antiretroviral activity
                          of the compound may be attributable to the
                          inhibition of phosphorylation by PKC during
                          viral infection of cells. The inactivation of
                          HIV by hypericin is dependent on the presence
                          of light. In one study natural hypericin was
                          provided in a single dose to mice 24 hours
                          after experimental infection with Friend
                          leukemia virus (FV). Treated mice survived
                          more than 240 days after infection as
                          compared with 15 to 30 days for untreated
                          controls. It has also been shown that
                          synthetic hypericin enters lymphocytes and
                          macrophages in vitro. In addition, hypericin
                          decreases HIV in vitro in whole blood
                          obtained from HIV infected individuals. A
                          phase I dose escalatory trial of synthetic
                          hypericin showed the serum half-life of the
                          compound was shorter than expected (about 24
                          hours). Preliminary pharmacokinetic data
                          indicate that oral bioavailability ranges
                          from 14-22%. [AmFAR Tx Dir 1995;7(4)] [Proc
                          Natl Acad Sci USA 1993 Jan 1;90(1)]
 DISEASES STUDIED/TREATED HIV infection [AmFAR Tx Dir 1995;7(4)] [Am J
                          Hosp Pharm 1994 Feb 15;51(4)]
 CLASSIFICATION CODE      Antiretroviral [AmFAR Tx Dir 1995;7(4)]
 CLASSIFICATION CODE      Antidepressant [Merck Index 1989]
 OTHER MAJOR USES         Antidepressant, astringent and diuretic
                          [Merck Index 1989] [The Extra Pharmacopoeia
                          1993]
 ADVERSE EFFECTS          Dose-limiting reversible photosensitivity,
                          requiring withdrawal of some patients, was
                          observed at 0.5 mg/kg. The reaction manifests
                          as a tingling or burning sensation in the
                          skin, or hypersensitivity to cold or hot.
                          Reversible elevated liver function tests have
                          been associated with over-the-counter
                          hypericin-containing extracts (St. John's
                          Wort). [AmFAR Tx Dir 1995;7(4)]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: An aromatic polycyclic
                          dione, extracted from the herb Hypericum
                          triquetrifolium Turra (St. John's Wort) by
                          several successive extractions followed by
                          chromatographic procedures [AmFAR Tx Dir
                          1995;7(4)]
 CHEMICAL/PHYSICAL DATA   MOLECULAR FORMULA: C30H16O8 [Merck Index
                          1989]
 CHEMICAL/PHYSICAL DATA   MOLECULAR WEIGHT: 504.43 [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   ELEMENTAL COMPOSITION: C71.43%, H3.20%,
                          O25.38% [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   SOLUBILITY: Freely soluble in pyridine and
                          other organic bases; almost insoluble in most
                          other organic solvents. Soluble in alkaline
                          aqueous solutions [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   PHYSICAL DESCRIPTION: Solvated blue-black
                          needles from pyridine and methanolic HCL
                          [Merck Index 1989]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Intravenous, oral. [AmFAR
                          Tx Dir 1995;7(4)]
 MANUFACTURERS            VIMRx
 REFERENCES               Steinbeck-Klose A, Wernet P. Successful long
                          term treatment over 40 months of HIV-patients
                          with intravenous Hypericin. Int Conf AIDS.
                          1993 Jun 6-11;9(1):470 (abstract no.
                          PO-B26-2012).
 REFERENCES               Hudson JB, Harris L, Towers GH. The
                          importance of light in the anti-HIV effect of
                          hypericin. Antiviral Res. 1993
                          Feb;20(2):173-8.
 REFERENCES               Lenard J, Rabson A, Vanderoef R. Photodynamic
                          inactivation of infectivity of human
                          immunodeficiency virus and other enveloped
                          viruses using hypericin and rose bengal:
                          inhibition of fusion and syncytia formation.
                          Proc Natl Acad Sci USA. 1993 Jan
                          1;90(1):158-62.
 REFERENCES               Furner V, Bek M, Gold J. A Phase I/II
                          unblinded dose ranging study of hypericin in
                          HIV-positive subjects. Int Conf AIDS. 1991
                          Jun 16-21;7(2):199 (abstract no. W.B.2071).
 REFERENCES               Cooper WC, James J. An observational study of
                          the efficacy of hypericin in HIV+ subjects.
                          Int Conf AIDS. 1990 Jun 20-23;6(2):369
                          (abstract no. 2063).
 ENTRY MONTH              9105
 LAST REVISION DATE       951031
 

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