      Document 0037
 DOCN  DRG0037
 UNIQUE IDENTIFIER        DRG-0210
 NAME OF SUBSTANCE        Vesnarinone [USAN 1996]
 REGISTRY NUMBER          81840-15-5
 STANDARD CHEMICAL NAME   Piperazine,
                          1-(3,4-dimethoxybenzoyl)-4-(1,2,3,4-tetrahydr-
                          o -2-oxo-6-quinolinyl)- [USAN 1996]
 SYNONYMS                 3,4-Dihydro-6-(4-(3,4-dimethoxybenzoyl)-1-pip-
                          erazinyl) -2(1H)-quinolinone [CHEMLINE]
 SYNONYMS                 Arkin-Z [Index Nominum 16th ed.]
 PROTOCOL ID NUMBERS      FDA 234A
 PROTOCOL ID NUMBERS      FDA 234B
 PROTOCOL ID NUMBERS      FDA 234C
 PROTOCOL ID NUMBERS      FDA 234D
 SECONDARY SOURCE ID      OPC-8212 [USAN 1996]
 SECONDARY SOURCE ID      OPC 8212 [CHEMLINE]
 PHARMACOLOGICAL ACTION   MODE OF ACTION: Inhibits both nucleoside and
                          nucleobase transport in mammalian cells.
                          Inhibits replication of HIV-1 in a peripheral
                          blood lymphocytes model and in chronically
                          infected macrophages at clinically achieved
                          concentrations. Vesnarinone has no direct
                          inhibitory activity against the reverse
                          transcriptase of HIV-1, syncytium formation
                          in short term assays, or retroviral protease.
                          In addition, vesnarinone inhibits production
                          of TNF-alpha and IL-6 by human peripheral
                          blood mononucleated cells stimulated with
                          lipopolysaccharide (LPS). [Biochem Biophys
                          Res Comm 1993 Sep 30;195(3)] [Life Sci 1995
                          Jun 30;57(6)]
 DISEASES STUDIED/TREATED Primary HIV infection [FDA 234A]
 CLASSIFICATION CODE      Antiretroviral [Biochem Biophys Res Comm 1993
                          Sep 30;195(3)]
 CLASSIFICATION CODE      Cardiotonic [USAN 1996]
 OTHER MAJOR USES         Congestive heart failure [Biochem Biophys Res
                          Comm 1993 Sep 30;195(3)]
 SUBSTANCE INTERACTIONS   Possibly interacts with nucleoside analog
                          antiretroviral agents such as AZT, ddI, and
                          ddC. [FDA 234A]
 ADVERSE EFFECTS          Adverse effects include neutropenia. [Am J
                          Cardiol 1994 Nov;74(9)]
 CONTRAINDICATIONS        Contraindicated in pregnant women. [FDA 234A]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: Synthesized quinolinone
                          derivative. An inotropic phosphodiesterase
                          inhibitor [Circulation 1994 Mar;89(3); Eur J
                          Pharmacol 1993 Aug 10;240(1)]
 CHEMICAL/PHYSICAL DATA   MOLECULAR FORMULA: C22H25N3O4 [USAN 1996]
 CHEMICAL/PHYSICAL DATA   MOLECULAR WEIGHT: 395.46 [USAN 1996]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: Tablets. [FDA 234A]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Oral. [FDA 234A]
 MANUFACTURERS            Otsuka America Pharmaceutical Inc
 REFERENCES               Zhan X, Yin G, Liu S. Kinetic study on the
                          photostability of solid vesnarinone and the
                          equivalent relationship between daylight and
                          lamplight. J Pharm Sci 1995 May;84(5):624-6.
 REFERENCES               Kumakura T, Takase K, Terada N, Gelfand EW.
                          Vesnarinone inhibits nucleoside and
                          nucleobase transport. Life Sci.
                          1995;57(6):PL75-81.
 REFERENCES               Mitsuyasu R, Bort L, Miles SA, Hardy WD,
                          Petit RG. Preliminary results of a phase I
                          study of vesnarinone (OPC-8212) in
                          HIV-infected persons with CD4 > 300
                          cells/MM3. Int Conf AIDS. 1994 Aug
                          7-12;10(1):8 (abstract no. 005B).
 REFERENCES               Maruyama Y, Kobayachi N, Maruyama I, Osame M.
                          Vesnarinone; a preliminary therapeutic
                          approach to HIV-1 infection. Int Conf AIDS.
                          1994 Aug 7-12;10(1):203 (abstract no.
                          PBO241).
 REFERENCES               Young NS. Agranulocytosis [clinical
                          conference]. JAMA 1994 Mar
                          23-30;271(12):935-8.
 REFERENCES               Uetrecht JP, Zahid N, Whitfield D. Metabolism
                          of vesnarinone by activated neutrophils:
                          implications for vesnarinone-induced
                          agranulocytosis. J Pharmacol Exp Ther; VOL
                          270,ISS 3,1994,P865-72.
 REFERENCES               Matsui S, Matsumori A, Matoba Y, Uchida A,
                          Sasayama S. Treatment of virus-induced
                          myocardial injury with a novel
                          immunomodulating agent, vesnarinone.
                          Suppression of natural killer cell activity
                          and tumor necrosis factor-alpha production. J
                          Clin Invest; VOL 94,ISS 3,1994,P1212-7.
 REFERENCES               Bertolet BD, White BG, Pepine CJ. Neutropenia
                          occurring during treatment with vesnarinone
                          [OPC-8212]. Am J Cardio. 1994;74(9):968-70.
 REFERENCES               Maruyama I, Maruyama Y, Nakajima T, Kitajima
                          I, Osame M, Zhao JQ, Chen IS, Nakai S, Ikeda
                          M, Yabu-uchi Y, et al. Vesnarinone inhibits
                          production of HIV-1 cultured cells. Biochem
                          Biophys Res Commun. 1993 Sep
                          30;195(3):1264-71.
 REFERENCES               Feldman AM, Bristow MR, Parmley WW, Carson
                          PE, Pepine CJ, Gilbert EM, Strobeck JE,
                          Hendrix GH, Powers ER, Bain RP, et al.
                          Effects of vesnarinone on morbidity and
                          mortality in patients with heart failure.
                          Vesnarinone Study Group [see comments]. N
                          Engl J Med 1993 Jul 15;329(3):149-55.
 ENTRY MONTH              9405
 LAST REVISION DATE       960424
 

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