Scripps VIVO scripps research logo

  • Index
  • Log in
  • Home
  • People
  • Organizations
  • Research
  • Events
Search form
As of April 1st VIVO Scientific Profiles will no longer updated for faculty, and the link to VIVO will be removed from the library website. Faculty profile pages will continue to be updated via Interfolio. VIVO will continue being used behind the scenes to update graduate student profiles. Please contact helplib@scripps.edu if you have questions.
How to download citations from VIVO | Alternative profile options

GalR2-positive allosteric modulator exhibits anticonvulsant effects in animal models

Academic Article
uri icon
  • Overview
  • Research
  • Identity
  • Additional Document Info
  • View All
scroll to property group menus

Overview

authors

  • Lu, Xiaoying
  • Roberts, Edward
  • Xia, F. C.
  • Sanchez-Alavez, Manuel
  • Liu, T. Y.
  • Baldwin, R.
  • Wu, S.
  • Chang, J.
  • Wasterlain, C. G.
  • Bartfai, Tamas

publication date

  • August 2010

journal

  • Proceedings of the National Academy of Sciences of the United States of America  Journal

abstract

  • Galanin receptors type 1 (GalR1) and/or type 2 (GalR2) represent unique pharmacological targets for treatment of seizures and epilepsy. Previous studies have shown that the endogenous peptide ligand galanin exerts powerful anticonvulsant effect through activation of these two G protein-coupled receptors, which are highly expressed in the temporal lobe of rodent brain. Here we report the characterization of a putative GalR2-positive allosteric modulator CYM2503. CYM2503 potentiated the galanin-stimulated IP1 accumulation in HEK293 cells stably expressing GalR2 receptor, whereas it exhibited no detectable affinity for the (125)I galanin-binding site of GalR2 receptor, an effect consistent with that of a positive allosteric modulator. In the rat Li-pilocarpine status epilepticus model, CYM2503, injected intraperitoneally, increased the latency to first electrographic seizure and the latency to first stage 3 behavioral seizure, decreased the latency to the establishment of status epilepticus, and dramatically decreased the mortality. In a Li-pilocarpine seizure model in mice, CYM2503 increased the latency to first electrographic seizure and decreased the total time in seizure. CYM2503 also attenuated electroshock-induced seizures in mice. Thus, CYM2503 provides a starting point for the development of anticonvulsant therapy using the galanin R2 receptor as target.

subject areas

  • Allosteric Regulation
  • Animals
  • Anticonvulsants
  • Carbamates
  • Cell Line
  • Dipeptides
  • Disease Models, Animal
  • Electroshock
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Pilocarpine
  • Quinolones
  • Rats
  • Rats, Wistar
  • Receptor, Galanin, Type 1
  • Receptor, Galanin, Type 2
  • Recombinant Proteins
  • Seizures
  • Signal Transduction
  • Status Epilepticus
scroll to property group menus

Research

keywords

  • G protein-coupled receptor
  • galanin
  • seizure
  • status epilepticus
scroll to property group menus

Identity

PubMed Central ID

  • PMC2930524

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.1008986107

PubMed ID

  • 20660766
scroll to property group menus

Additional Document Info

start page

  • 15229

end page

  • 15234

volume

  • 107

issue

  • 34

©2022 The Scripps Research Institute | Terms of Use | Powered by VIVO

  • About
  • Contact Us
  • Support