Literature DB >> 24900783

Qualification of LSP1-2111 as a Brain Penetrant Group III Metabotropic Glutamate Receptor Orthosteric Agonist.

Manuel Cajina1, Megan Nattini1, Dekun Song1, Gennady Smagin1, Erling B Jørgensen2, Gamini Chandrasena1, Christoffer Bundgaard2, Dorthe Bach Toft2, Xinyan Huang1, Francine Acher3, Dario Doller1.   

Abstract

LSP1-2111 is a group III metabotropic glutamate receptor agonist with preference toward the mGlu4 receptor subtype. This compound has been extensively used as a tool to explore the pharmacology of mGlu4 receptor activation in preclinical animal behavioral models. However, the blood-brain barrier penetration of this amino acid derivative has never been studied. We report studies on the central nervous system (CNS) disposition of LSP1-2111 using quantitative microdialysis in rat. Significant unbound concentrations of the drug relative to its in vitro binding affinity and functional potency were established in extracellular fluid (ECF). These findings support the use of LSP1-2111 to study the CNS pharmacology of mGlu4 receptor activation through orthosteric agonist mechanisms.

Entities:  

Keywords:  G protein-coupled receptors; Metabotropic glutamate receptors; mGlu4 receptor; orthosteric agonist

Year:  2013        PMID： 24900783      PMCID： PMC4027608          DOI： 10.1021/ml400338f

Source DB:  PubMed          Journal:  ACS Med Chem Lett        ISSN： 1948-5875            Impact factor:   4.345


  21 in total

1.  A novel selective metabotropic glutamate receptor 4 agonist reveals new possibilities for developing subtype selective ligands with therapeutic potential.

Authors:  Cyril Goudet; Bruno Vilar; Tiphanie Courtiol; Thierry Deltheil; Thomas Bessiron; Isabelle Brabet; Nadia Oueslati; Delphine Rigault; Hugues-Olivier Bertrand; Heather McLean; Hervé Daniel; Marianne Amalric; Francine Acher; Jean-Philippe Pin
Journal:  FASEB J       Date:  2012-01-05       Impact factor: 5.191

Review 2.  Recent advances in the drug discovery of metabotropic glutamate receptor 4 (mGluR4) activators for the treatment of CNS and non-CNS disorders.

Authors:  Sylvain Célanire; Brice Campo
Journal:  Expert Opin Drug Discov       Date:  2012-02-14       Impact factor: 6.098

Review 3.  The effect of plasma protein binding on in vivo efficacy: misconceptions in drug discovery.

Authors:  Dennis A Smith; Li Di; Edward H Kerns
Journal:  Nat Rev Drug Discov       Date:  2010-12       Impact factor: 84.694

4.  Synthesis and metabotropic glutamate receptor activity of S-oxidized variants of (-)-4-amino-2-thiabicyclo-[3.1.0]hexane-4,6-dicarboxylate: identification of potent, selective, and orally bioavailable agonists for mGlu2/3 receptors.

Authors:  James A Monn; Steven M Massey; Matthew J Valli; Steven S Henry; Gregory A Stephenson; Mark Bures; Marc Hérin; John Catlow; Deborah Giera; Rebecca A Wright; Bryan G Johnson; Sherri L Andis; Ann Kingston; Darryle D Schoepp
Journal:  J Med Chem       Date:  2007-01-25       Impact factor: 7.446

5.  Translational neuropharmacology and the appropriate and effective use of animal models.

Authors:  A R Green; J Gabrielsson; K C F Fone
Journal:  Br J Pharmacol       Date:  2011-10       Impact factor: 8.739

Review 6.  Optimising in vivo pharmacology studies--Practical PKPD considerations.

Authors:  Johan Gabrielsson; A Richard Green; Piet H Van der Graaf
Journal:  J Pharmacol Toxicol Methods       Date:  2010-02-11       Impact factor: 1.950

7.  Determination of gallium concentration in "blood-free" tissues using a radiolabeled blood marker.

Authors:  J W Triplett; T L Hayden; L K McWhorter; S R Gautam; E E Kim; D W Bourne
Journal:  J Pharm Sci       Date:  1985-09       Impact factor: 3.534

8.  Role of mGluR4 in acquisition of fear learning and memory.

Authors:  Matthew J Davis; Ovidiu D Iancu; Francine C Acher; Blair M Stewart; Massarra A Eiwaz; Robert M Duvoisin; Jacob Raber
Journal:  Neuropharmacology       Date:  2012-08-02       Impact factor: 5.250

9.  Activation of metabotropic glutamate 4 receptors decreases L-DOPA-induced dyskinesia in a mouse model of Parkinson's disease.

Authors:  Sébastien Lopez; Alessandra Bonito-Oliva; Simone Pallottino; Francine Acher; Gilberto Fisone
Journal:  J Parkinsons Dis       Date:  2011       Impact factor: 5.568

10.  A high content screening assay to predict human drug-induced liver injury during drug discovery.

Authors:  Mikael Persson; Anni F Løye; Tomas Mow; Jorrit J Hornberg
Journal:  J Pharmacol Toxicol Methods       Date:  2013-08-08       Impact factor: 1.950
View more
  8 in total

1.  Pharmacological stimulation of metabotropic glutamate receptor type 4 in a rat model of Parkinson's disease and L-DOPA-induced dyskinesia: Comparison between a positive allosteric modulator and an orthosteric agonist.

Authors:  Hanna Iderberg; Natallia Maslava; Analisa D Thompson; Michael Bubser; Colleen M Niswender; Corey R Hopkins; Craig W Lindsley; P Jeffrey Conn; Carrie K Jones; M Angela Cenci
Journal:  Neuropharmacology       Date:  2015-03-04       Impact factor: 5.250

2.  Re-exploring the N-phenylpicolinamide derivatives to develop mGlu4 ligands with improved affinity and in vitro microsomal stability.

Authors:  Zhaoda Zhang; Kun-Eek Kil; Pekka Poutiainen; Ji-Kyung Choi; Hye-Jin Kang; Xi-Ping Huang; Bryan L Roth; Anna-Liisa Brownell
Journal:  Bioorg Med Chem Lett       Date:  2015-07-17       Impact factor: 2.823

3.  Synthesis and evaluation of N-(methylthiophenyl)picolinamide derivatives as PET radioligands for metabotropic glutamate receptor subtype 4.

Authors:  Kun-Eek Kil; Pekka Poutiainen; Zhaoda Zhang; Aijun Zhu; Darshini Kuruppu; Shilpa Prabhakar; Ji-Kyung Choi; Bakhos A Tannous; Anna-Liisa Brownell
Journal:  Bioorg Med Chem Lett       Date:  2015-11-10       Impact factor: 2.823

4.  Synthesis and Characterization of Fluorine-18-Labeled N-(4-Chloro-3-((fluoromethyl-d2)thio)phenyl)picolinamide for Imaging of mGluR4 in Brain.

Authors:  Junfeng Wang; Xiying Qu; Timothy M Shoup; Gengyang Yuan; Sepideh Afshar; Chuzhi Pan; Aijun Zhu; Ji-Kyung Choi; Hye Jin Kang; Pekka Poutiainen; Georges El Fakhri; Zhaoda Zhang; Anna-Liisa Brownell
Journal:  J Med Chem       Date:  2020-03-04       Impact factor: 7.446

Review 5.  Metabotropic Glutamate Receptor 7: From Synaptic Function to Therapeutic Implications.

Authors:  Enza Palazzo; Ida Marabese; Vito de Novellis; Francesco Rossi; Sabatino Maione
Journal:  Curr Neuropharmacol       Date:  2016       Impact factor: 7.363

6.  Mutual activation of glutamatergic mGlu4 and muscarinic M4 receptors reverses schizophrenia-related changes in rodents.

Authors:  Paulina Cieślik; Monika Woźniak; Jerri M Rook; Mohammed N Tantawy; P Jeffrey Conn; Francine Acher; Krzysztof Tokarski; Magdalena Kusek; Andrzej Pilc; Joanna M Wierońska
Journal:  Psychopharmacology (Berl)       Date:  2018-07-27       Impact factor: 4.530

7.  The antipsychotic-like effects in rodents of the positive allosteric modulator Lu AF21934 involve 5-HT1A receptor signaling: mechanistic studies.

Authors:  Joanna M Wierońska; Anna Sławińska; Magdalena Łasoń-Tyburkiewicz; Piotr Gruca; Mariusz Papp; Stevin H Zorn; Darío Doller; Natalia Kłeczek; Karolina Noworyta-Sokołowska; Krystyna Gołembiowska; Andrzej Pilc
Journal:  Psychopharmacology (Berl)       Date:  2014-07-11       Impact factor: 4.530

8.  Involvement of GABAB Receptor Signaling in Antipsychotic-like Action of the Novel Orthosteric Agonist of the mGlu4 Receptor, LSP4-2022.

Authors:  Monika Woźniak; Francine Acher; Marcin Marciniak; Magdalena Lasoń-Tyburkiewicz; Piotr Gruca; Mariusz Papp; Andrzej Pilc; Joanna M Wierońska
Journal:  Curr Neuropharmacol       Date:  2016       Impact factor: 7.363
  8 in total

北京卡尤迪生物科技股份有限公司 © 2022-2023.