生物活性

• 描述Pridopidine exhibits high affinity towards sigma 1 receptor (S1R) (Ki = 70-80 nM) which can counteract the effects of excessive or insufficient dopaminergic transmission and it can be used as a dopamine (DA) stabilizer. Pridopidine displays about 100-fold higher affinity for the sigma-1 receptor (sigma-1R). Pridopidine slows disease progression and improves motor function in Huntington's disease model mice and, in preliminarily reports, Huntington's disease patients. Pridopidine exerts anti-amnesic and potentially neuroprotective actions^[1]. Oral pridopidine treatment rescued mushroom spines in vivo in aged PS1-KI-GFP mice. Pridopidine stabilizes mushroom spines in mouse models of AD and this requires S1R, endoplasmic reticulum calcium leakage through PS1/2 and nSOC(neuronal store-operated calcium entry)^[2]. By 5 weeks of daily administration, a low dose of pridopidine (0.3 mg/kg) had significantly improved deficits in forelimb use (cylinder test, stepping test) and abolished the ipsilateral rotational bias typical of hemiparkinsonian animals. A higher dose of pridopidine (1 mg/kg) significantly improved only the rotational bias, with a trend towards improvement in forelimb use. The behavioral recovery induced by pridopidine 0.3 mg/kg was accompanied by a significant protection of nigral dopamine cell bodies, an increased dopaminergic fiber density in the striatum, and striatal upregulation of GDNF, BDNF, and phosphorylated ERK1/2^[3].
• 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
  NCT00665223	Huntington's Disease	Phase 3	Completed	-	Austria ... more >> LKH -Univ. Klinikum Graz, Universitaetsklinik fur Psychiatrie Graz Graz, Styria, Austria, 8036 Innsbruck Medical University, Anichstraße 35 Innsbruck, Tyrol, Austria, A-6020 Belgium University Hospital Gasthuisberg Leuven, Flemish Brabant, Belgium, 3000 France Hôpital Purpan, Place Docteur-Baylac, Bâtiment F Toulouse Cedex 9, Midi-Pyrénées region, France, 31059 CHU Roger Salengro Lille Cedex, Nord-Pas de Calais, France, 59037 Hôpital Nord, CHU d'Amiens, Service de Neurologie Amiens Cedex 1, Picardie, France, 80054 CHU La Timone, 264 Rue Saint Pierre Marseille Cedex 05, Provence-Alpes-Cote d'Azur, France, 13385 Germany Universitätsklinik Ulm, Neurologie/ Oberer Eselberg 45/1 Ulm, Baden-Württemberg, Germany, 89081 Klinikum rechts der Isar der Technischen Universität München, Neurologische Klinik und Poliklinik, Ismaninger Str. 22 München, Bavaria, Germany, 81675 Isar Amper Klinikum gemeinnützige GmbH, Klinik Taufkirchen (Vils), Bräuhausstr.5 Taufkirchen (Vils), Bavaria, Germany, 84416 St. Josef Hospital, Ruhr University Bochum, Gudrunstraße 56 Bochum, North Rhine-Westphalia, Germany, 44791 Westfaelische Wilhelms-Universitaet Muenster, Klinik fur Neurologie Muenster, North Rhine-Westphalia, Germany, 48149 Universitat Dresden, Klinikum Carl Gustav Carus, Fetscherstr. 74 Dresden, Saxony, Germany, 01307 Klinik für Psychiatrie und Psychotherapie, Charité - Universitätsmedizin Berlin, Schumannstrasse 20/21 Berlin, Germany, 10117 Italy Fondazione IRCCS Istituto Nazionale Neurologico "Carlos Besta", Department of Movement Disorders, 11 via Celoria Milano, Lombardy, Italy, 20133 IRCCS Neuromed, Localita Camarelle Pozzilli, Molise, Italy, 86077 Portugal University Hospital of Coimbra, Av. Rissaya Barreto Coimbra, Baixo Mondego, Portugal, 3000-075 Centro de Estudos Egas Moniz, Faculdade de Medicina de Lisboa, Av. Prof. Egas Moniz Lisboa, Portugal, 1649-028 Spain Hospital Mútua de Terrassa, C/ Castell Terrassa, Catalonia, Spain, 08225 Hospital Clinic of Barcelona, Calle Villarroel, 170 Barcelona, Spain, 08036 Hospital Ramon y Cajal, Carretera Colemenar km 9.100 Madrid, Spain, 28034 Hospital Universitario La Fe, Avda. Campanar 21, Valencia, Spain, 46009 United Kingdom R&D Headquarters, Barberry Centre, 25 Vincent Drive Birmingham, England/West Midlands, United Kingdom, B15 2SG Department of Clinical Genetics, St Mary's Hospital, Hathersage Road Manchester, North West England, United Kingdom, M13 9WL First Floor Argyll House, Fosterhill, Cornhill Road Aberdeen, Scotland, United Kingdom, AB25 2ZR SE Scotland Genetic Service, Western General Hospital, Crewe Road Edinburgh, Scotland, United Kingdom, EH4 2XU Churchill Hospital, Old Road, Headington Oxford, South East England, United Kingdom, OX3 7LJ Academic Neurology Unit, E Floor Medical School Beech Hill Road Sheffield, South Yorkshire, United Kingdom, S10 2RX Institute of Human Genetics, Centre for Life, Central Parkway Newcastle on Tyne, Tyne and Wear, United Kingdom, NE1 3BZ Cardiff University School of Medicine, Department of Neurology & Medical Genetics, Heath Park Cardiff, Wales, United Kingdom, CF14 4XN Cambridge Centre for Brain repair, Cambridge University Cambridge, United Kingdom, CB2 2PY Collapse <<
  NCT02006472	Huntington's Disease	Phase 2	Completed	-	-
  NCT01306929	Huntington Disease	Phase 2	Completed	-	United States, Indiana ... more >> Teva Investigational Site 045 Indianapolis, Indiana, United States, 46202 United States, Iowa Teva Investigational Site 024 Iowa City, Iowa, United States, 52242 United States, Maryland Teva Investigational Site 028 Baltimore, Maryland, United States, 21287 United States, New York Teva Investigational Site 037 Albany, New York, United States, 12208 Teva Investigational Site 001 Rochester, New York, United States, 14620 United States, Ohio Teva Investigational Site 089 Cincinnati, Ohio, United States, 45267 United States, Pennsylvania Teva Investigational Site 018 Philadelphia, Pennsylvania, United States, 19107 United States, Washington Teva Investigational Site 220 Kirkland, Washington, United States, 98034 Canada, British Columbia Teva Investigational Site 048 Vancouver, British Columbia, Canada, V6T 2B5 Canada, Ontario Teva Investigational Site 231 Ottawa, Ontario, Canada, K1G 4G3 Canada Teva Investigational Site 118 London, Canada, N6A 5A5 Teva Investigational Site 039 Toronto, Canada, M3B 2S7 Collapse <<

• 更多
• 参考文献

• [1] Sahlholm K, Valle-León M, Fernández-Dueñas V, Ciruela F. Pridopidine Reverses Phencyclidine-Induced Memory Impairment. Front Pharmacol. 2018 Apr 10;9:338

  [2] Ryskamp D, Wu L, Wu J, Kim D, Rammes G, Geva M, Hayden M, Bezprozvanny I. Pridopidine stabilizes mushroom spines in mouse models of Alzheimer's disease by acting on the sigma-1 receptor. Neurobiol Dis. 2019 Apr;124:489-504

  [3] Francardo V, Geva M, Bez F, Denis Q, Steiner L, Hayden MR, Cenci MA. Pridopidine Induces Functional Neurorestoration Via the Sigma-1 Receptor in a Mouse Model of Parkinson's Disease. Neurotherapeutics. 2019 Apr;16(2):465-479