ArticleProceedings of the National Academy of Sciences of the United States of America2010
GalR2-positive allosteric modulator exhibits anticonvulsant effects in animal models.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
13 citing papers in PubMed, 32 citations in OpenAlex.
- Insights into Potential Targets for Therapeutic Intervention in Epilepsy.International journal of molecular sciences · 2020Review
- Neuropeptide and Small Transmitter Coexistence: Fundamental Studies and Relevance to Mental Illness.Frontiers in neural circuits · 2018Review
- GPCR Allosteric Modulators: Mechanistic Advantages and Therapeutic Applications.Current topics in medicinal chemistry · 2018Article
- Homology modeling, docking, and molecular dynamics simulation of the receptor GALR2 and its interactions with galanin and a positive allosteric modulator.Journal of molecular modeling · 2016Article
- Efficacy and tolerability of the galanin analog NAX 5055 in the multiple-hit rat model of symptomatic infantile spasms.Epilepsy research · 2014Article
- Positive allosteric modulators to peptide GPCRs: a promising class of drugs.Acta pharmacologica Sinica · 2013Review
- Receptor subtype-dependent galanin actions on gamma-aminobutyric acidergic neurotransmission and ethanol responses in the central amygdala.Addiction biology · 2012Article
- Galanin receptors and ligands.Frontiers in endocrinology · 2012Article
- Synthesis and biological evaluation of novel pyrimidine derivatives as sub-micromolar affinity ligands of GalR2.Bioorganic & medicinal chemistry letters · 2011Article
- Rap1 mediates galanin receptor 2-induced proliferation and survival in squamous cell carcinoma.Cellular signalling · 2011Article
- Endogenous galanin protects mouse hippocampal neurons against amyloid toxicity in vitro via activation of galanin receptor-2.Journal of Alzheimer's disease : JAD · 2011Article
- From the bench to the bedside: Spinal cord regeneration, niacin for stroke, magnetic nanoparticles, stimulation for epilepsy, role of galanins in epilepsy, functions of the supramarginal gyri, and the role of inflammation in postoperative cognitive disturbances.Surgical neurology international · 2010Article
- Neuropeptide receptor positive allosteric modulation in epilepsy: galanin modulation revealed.Proceedings of the National Academy of Sciences of the United States of America · 2010Article
Corrections and comments
- Commented on by
Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
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.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.