Synthesis and N-Methyl-D-aspartate (NMDA) Receptor Activity of Ketamine Metabolites

被引:65
作者
Morris, Patrick J. [1 ]
Moaddel, Ruin [2 ]
Zanos, Panos [3 ]
Moore, Curtis E. [4 ]
Gould, Todd [3 ,5 ,6 ]
Zarate, Carlos A., Jr. [7 ]
Thomas, Craig J. [1 ]
机构
[1] NIH, Div Preclin Innovat, Natl Ctr Adv Translat Sci, Rockville, MD 20850 USA
[2] NIA, Biomed Res Ctr, NIH, Baltimore, MD 21224 USA
[3] Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21201 USA
[4] Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA
[5] Univ Maryland, Sch Med, Dept Pharmacol, Baltimore, MD 21201 USA
[6] Univ Maryland, Sch Med, Dept Anat & Neurobiol, Baltimore, MD 21201 USA
[7] NIMH, Expt Therapeut & Pathophysiol Branch, NIH, Bethesda, MD 20892 USA
关键词
ANTIDEPRESSANT; MECHANISMS; DEPRESSION; AMINATION; CURRENTS; PLASMA;
D O I
10.1021/acs.orglett.7b02177
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
Ketamine is rapidly metabolized in the human body to a variety of metabolites, including the hydroxynorketamines. At least two hydroxynorketamines have significant antidepressant action in rodent models, with limited action against the N-methyl-D-aspartate (NMDA) receptor. The synthesis of 12 hydroxynorketamines and their binding affinity to the NMDA receptor is presented here.
引用
收藏
页码:4572 / 4575
页数:4
相关论文
共 23 条
  • [1] Berman F W, 1996, J Biochem Toxicol, V11, P217, DOI 10.1002/(SICI)1522-7146(1996)11:5<217::AID-JBT2>3.0.CO
  • [2] 2-N
  • [3] Asymmetric synthesis of (S)- and (R)-norketamine via Sharpless asymmetric dihydroxylation/Ritter amination sequence
    Biermann, Manfred
    Zheng, Guangrong
    Hojahmat, Marhaba
    Moskalev, Nick V.
    Crooks, Peter A.
    [J]. TETRAHEDRON LETTERS, 2015, 56 (20) : 2608 - 2610
  • [4] The use of ketamine as an antidepressant: a systematic review and meta-analysis
    Coyle, Caoimhe M.
    Laws, Keith R.
    [J]. HUMAN PSYCHOPHARMACOLOGY-CLINICAL AND EXPERIMENTAL, 2015, 30 (03) : 152 - 163
  • [5] Emerging mechanisms and treatments for depression beyond SSRIs and SNRIs
    Dale, Elena
    Bang-Andersen, Benny
    Sanchez, Connie
    [J]. BIOCHEMICAL PHARMACOLOGY, 2015, 95 (02) : 81 - 97
  • [6] MOLECULAR DESIGN OF THE N-METHYL-D-ASPARTATE RECEPTOR-BINDING SITE FOR PHENCYCLIDINE AND DIZOLCIPINE
    FERRERMONTIEL, AV
    SUN, W
    MONTAL, M
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (17) : 8021 - 8025
  • [7] STEREOCHEMICAL STUDIES OF DEMETHYLATED KETAMINE ENANTIOMERS
    HONG, SC
    DAVISSON, JN
    [J]. JOURNAL OF PHARMACEUTICAL SCIENCES, 1982, 71 (08) : 912 - 914
  • [8] COMPARATIVE PHARMACOLOGY IN THE RAT OF KETAMINE AND ITS 2 PRINCIPAL METABOLITES, NORKETAMINE AND (Z)-6-HYDROXYNORKETAMINE
    LEUNG, LY
    BAILLIE, TA
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 1986, 29 (11) : 2396 - 2399
  • [9] Sub-anesthetic concentrations of (R,S)-ketamine metabolites inhibit acetylcholine-evoked currents in α7 nicotinic acetylcholine receptors
    Moaddel, Ruin
    Abdrakhmanova, Galia
    Kozak, Joanna
    Jozwiak, Krzysztof
    Toll, Lawrence
    Jimenez, Lucita
    Rosenberg, Avraham
    Tran, Thao
    Xiao, Yingxian
    Zarate, Carlos A.
    Wainer, Irving W.
    [J]. EUROPEAN JOURNAL OF PHARMACOLOGY, 2013, 698 (1-3) : 228 - 234
  • [10] A parallel chiral-achiral liquid chromatographic method for the determination of the stereoisomers of ketamine and ketamine metabolites in the plasma and urine of patients with complex regional pain syndrome
    Moaddel, Ruin
    Venkata, Swarajya Lakshmi Vattem
    Tanga, Mary J.
    Bupp, James E.
    Green, Carol E.
    Iyer, Lalitha
    Furimsky, Anna
    Goldberg, Michael E.
    Torjman, Marc C.
    Wainer, Irving W.
    [J]. TALANTA, 2010, 82 (05) : 1892 - 1904