生物活性

• 描述(R)-Baclofen(STX209) is a selective GABAB receptor agonist. Basal protein synthesis, which is elevated in the hippocampus of Fmr1-knockout mice, was corrected by the in vitro application of the selective GABA(B) receptor agonist STX209 (arbaclofen, R-baclofen). Acute administration of STX209 in vivo, at doses that modify behavior, decreased mRNA translation in the cortex of Fmr1-knockout mice^[3]. Acute R-baclofen administration corrected elevated protein synthesis and reduced deficits on a test of social behavior in adult Fmr1 KO mice. It also suppressed activity of the mammalian target of rapamycin pathway, particularly in synaptosome-enriched fractions, but it had no effect on extracellular-regulated kinase 1/2 activity^[4]. R-baclofen treatment reversed social approach deficits in BTBR T+ Itpr3tf/J (BTBR), reduced repetitive self-grooming and high marble burying scores in BTBR, and reduced stereotyped jumping in C58/J (C58), at nonsedating doses^[5]. Moreover, chronic activation of GABAB receptors improved performance on a series of cognitive and social tasks known to be impaired in two different 16p11.2 deletion mouse models^[6].
• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT02462317	Muscle Spasticity	Phase 4	Recruiting	September 2020	France ... more >> University Hospital, Toulouse Recruiting Toulouse, Haute-Garonne, France, 31059 Contact: Philippe MARQUE, MD PHD    5 61 32 28 01 ext 33    marque.ph@chu-toulouse.fr    Principal Investigator: Philippe MARQUE, MD PHD          CHU Jean Minjoz Not yet recruiting Besançon, France, 25030 Contact: Bernard PARRATTE, MD PHD    3 63 08 25 51 ext 33    bernard.parratte@univfcomte.fr    Groupe Pellegrin, University Hospital Bordeaux Not yet recruiting Bordeaux, France, 33076 Contact: Patrick DEHAIL, PHD MD    556796006 ext 33    patrick.dehail@chubordeaux.fr    Centre de rééducation MARIENIA Not yet recruiting Cambo Les Bains, France, 64250 Contact: Michel BEGUE, MD    559936801 ext 33    m.begue@marienia.fr    Centre Bouffard- Vercelli Not yet recruiting Cerbere, France, 66290 Contact: Michel ENJALBERT, MD    4 68 88 75 00 ext 33    michel.enjalbert@wanadoo.fr    University Hospital Dijon Not yet recruiting Dijon, France, 21079 Contact: Charles BENAIM, MD PHD    380293643 ext 33    charles.benaim@chu-dijon.fr    University Hospital Grenoble Not yet recruiting Echirolles, France, 38434 Contact: Dominic PERENNOU, MD PHD    4 76 76 60 83 ext 33    DPerennou@chu-grenoble.fr    Hôpital R. Poincarré Not yet recruiting Garches, France, 92380 Contact: Alexis SCHNITZER, MD    1 47 10 77 26 ext 33    alexis.schnitzler@rpc.aphp.fr    Hôpital Swynghedauw Not yet recruiting Lille, France, 59000 Contact: Etienne ALLART, MD    3-20-44-58-32 ext 33    Etienne.ALLART@CHRU-LILLE.FR    Hôpital J Rebeyrol Not yet recruiting Limoges, France, 87042 Contact: Jean- Christophe DAVIET, MD PHD    5 55 05 65 13 ext 33    jean-Christophe.Daviet@chu-limoges.fr    CHU Gui de Chauliac Not yet recruiting Montpellier, France, 34295 Contact: Isabelle LAFFOND, MD    4 67 33 87 17 ext 33    i-laffont@chu-montpellier.fr    University Hospital Carémeau Not yet recruiting Nimes, France, 30029 Contact: Frédéric PELLAS, MD PHD    4 66 68 34 59 ext 33    frederic.pellas@chu-nimes.fr    Hopital Rothschild Not yet recruiting Paris, France, 75012 Contact: Gilberte ROBAIN, MD PHD    1 49 59 46 97 ext 33    gilberte.robain@rth.aphp.fr    GH Lariboisière F.Widal Not yet recruiting Paris, France, 75013 Contact: Alain YELNIK, MD PHD    1 40 05 48 51 ext 33    alain.yelnik@lrb.aphp.fr    Groupe Hospitalier Pitié-Salpêtrière Not yet recruiting Paris, France, 75013 Contact: Dominique MAZEVET, MD    1 42 16 11 48 ext 33    dominique.mazevet@psl.aphp.fr    Université Reims Champagne Ardenne Not yet recruiting Reims, France, 51092 Contact: François BOYER, MD PHD    3 26 78 44 80 ext 33    fboyer@chu-reims.fr    Pôle MPR St Hélier Not yet recruiting Rennes, France, 35000 Contact: Philippe GALLIEN, MD    2 99 29 50 80 ext 33    philippe.gallien@polesthelier.com Collapse <<
  NCT02511886	Alcohol Use Disorder	Phase 2	Completed	-	United States, Florida ... more >> Research Centers of America Oakland Park, Florida, United States, 33334 Collapse <<
  NCT01520545	Severe Spasticity	Phase 3	Completed	-	United States, Arkansas ... more >> Arkansas Children's Hospital Little Rock, Arkansas, United States, 72202 United States, California Loma Linda University Loma Linda, California, United States, 92354 United States, Florida Rehabilitation Medicine Department, University of Miami, Miller School of Medicine Miami, Florida, United States, 33136 United States, Illinois Rehabilitation Institute of Chicago Chicago, Illinois, United States, 60611 United States, Michigan Wayne State University, School of Medicine Dearborn, Michigan, United States, 48124 United States, Minnesota Gillette Children's Specialty Healthcare Saint Paul, Minnesota, United States, 55101 United States, Ohio Cleveland Clinic Foundation Cleveland, Ohio, United States, 44195 The Ohio State University Columbus, Ohio, United States, 43221 United States, Tennessee Vanderbilt University Medical Center, Department of Pediatrics Nashville, Tennessee, United States, 37232 United States, Texas Cook Children's Health Care System Fort Worth, Texas, United States, 76104 TIRR Memorial Hermann Houston, Texas, United States, 77030 United States, Utah University of Utah, Division of PM&R Salt Lake City, Utah, United States, 84132 United States, Wisconsin The Medical College of Wisconsin Department of Physical Medicine and Rehabilitation Milwaukee, Wisconsin, United States, 53226 Collapse <<

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• 参考文献

• [1] Falch E, Hedegaard A, et al. Comparative stereostructure-activity studies on GABAA and GABAB receptor sites and GABA uptake using rat brain membrane preparations. J Neurochem. 1986 Sep;47(3):898-903.

  [2] Penn RD, Kroin JS. Intrathecal baclofen alleviates spinal cord spasticity. Lancet. 1984 May 12;1(8385):1078.

  [3] Henderson C, Wijetunge L, Kinoshita MN, Shumway M, Hammond RS, Postma FR, Brynczka C, Rush R, Thomas A, Paylor R, Warren ST, Vanderklish PW, Kind PC, Carpenter RL, Bear MF, Healy AM. Reversal of disease-related pathologies in the fragile X mouse model by selective activation of GABAB receptors with arbaclofen. Sci Transl Med. 2012 Sep 19;4(152):152ra128

  [4] Qin M, Huang T, Kader M, Krych L, Xia Z, Burlin T, Zeidler Z, Zhao T, Smith CB. R-Baclofen Reverses a Social Behavior Deficit and Elevated Protein Synthesis in a Mouse Model of Fragile X Syndrome. Int J Neuropsychopharmacol. 2015 Mar 28;18(9):pyv034

  [5] Silverman JL, Pride MC, Hayes JE, Puhger KR, Butler-Struben HM, Baker S, Crawley JN. GABAB Receptor Agonist R-Baclofen Reverses Social Deficits and Reduces Repetitive Behavior in Two Mouse Models of Autism. Neuropsychopharmacology. 2015 Aug;40(9):2228-39

  [6] Stoppel LJ, Kazdoba TM, Schaffler MD, Preza AR, Heynen A, Crawley JN, Bear MF. R-Baclofen Reverses Cognitive Deficits and Improves Social Interactions in Two Lines of 16p11.2 Deletion Mice. Neuropsychopharmacology. 2018 Feb;43(3):513-524

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