Imaging of Metabotropic Glutamate Receptors (mGluRs)

Zhang, Zhaoda; Brownell, Anna‐Liisa

doi:10.5772/23714

Cited by 11 publications

(14 citation statements)

References 134 publications

(81 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Corresponding selective tools are, therefore, missing presently and are really needed to clarify roles of the two group II mGlu in the therapeutic indications discussed in the present article, as well as to unveil additional therapeutic potentials of group II mGluR blockers. Furthermore, compounds with high affinity for mGlus have been developed as positron emission tomography (PET) ligands to study receptor distribution and occupancy in the human brain, thus demonstrating the potential of mGlu modulation for the development of new drugs [93]. Although the first PET tracers based on an mGlu2 PAM scaffold were recently reported by Janssen Pharmaceuticals [4,94,95], no corresponding ligand based on an mGlu2 NAM scaffold has been described so far.…”

Section: Expert Opinionmentioning

confidence: 99%

Novel metabotropic glutamate receptor 2/3 antagonists and their therapeutic applications: a patent review (2005 – present)

Célanire

Sebhat

Wichmann

et al. 2014

Expert Opinion on Therapeutic Patents

View full text Add to dashboard Cite

show abstract

Section: Expert Opinionmentioning

confidence: 99%

Novel metabotropic glutamate receptor 2/3 antagonists and their therapeutic applications: a patent review (2005 – present)

Célanire

Sebhat

Wichmann

et al. 2014

Expert Opinion on Therapeutic Patents

View full text Add to dashboard Cite

show abstract

“…The binding of 4 was significantly increased compared to reference compound [ 3 H] 3 with higher concentration of glutamate. (d) Relative inhibition curve analysis of known mGlu4 targeting compounds (Engers et al, 2009)(Zhang and Brownell, 2012). …”

Section: Highlightsmentioning

confidence: 99%

Co-operative binding assay for the characterization of mGlu4 allosteric modulators

et al. 2015

Self Cite

View full text Add to dashboard Cite

The interest in the role of metabotropic glutamate receptor 4 (mGlu4) in CNS related disorders has increased the need for methods to investigate the binding of allosteric drug candidates. Our aim is to present the first fully characterized in vitro binding assay of mGlu4 positive allosteric modulators (PAMs). Results suggest that mGlu4 PAMs have characteristic co-operative binding with orthosteric glutamate, which offers a notable insight to the further development of mGlu4 targeted therapies.

show abstract

“…14 There has been substantial progress in identifying PAMs for mGlu 4 , and hundreds of mGlu 4 PAMs have been reported and/or patented since 2009. 5, 15, 16 Fig. 1 shows representative mGlu 4 PAMs.…”

mentioning

confidence: 99%

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

Kil

Poutiainen

Zhang

et al. 2016

Bioorganic & Medicinal Chemistry Letters

Self Cite

View full text Add to dashboard Cite

In recent years, mGlu4 has received great research attention because of the potential benefits of mGlu4 activation in treating numerous brain disorders, such as Parkinson’s disease (PD). A specific mGlu4 PET radioligand could be an important tool in understanding the role of mGlu4 in both healthy and disease conditions, and also for the development of new drugs. In this study, we synthesized four new N-(methylthiophenyl)picolinamide derivatives 11–14. Of these ligands, 11 and 14 showed high in vitro binding affinity for mGlu4 with IC50 values of 3.4 nM and 3.1 nM, respectively, and suitable physicochemical parameters. Compound 11 also showed enhanced metabolic stability and good selectivity to other mGluRs. [11C]11 and [11C]14 were radiolabeled using the [11C]methylation of the thiophenol precursors 20a and 20c with [11C]CH3I in 19.0% and 34.8% radiochemical yields (RCY), and their specific activities at the end of synthesis (EOS) were 496 ± 138 GBq/μmol (n=6) and 463 ± 263 GBq/μmol (n=4), respectively. The PET studies showed that [11C]11 accumulated fast into the brain and had higher uptake, slower washout and 25% better contrast than [11C]2, indicating improved imaging characteristics as PET radiotracer for mGlu4 compared to [11C]2. Therefore, [11C]11 will be a useful radioligand to investigate mGlu4 in different biological applications.

show abstract

Imaging of Metabotropic Glutamate Receptors (mGluRs)

Cited by 11 publications

References 134 publications

Novel metabotropic glutamate receptor 2/3 antagonists and their therapeutic applications: a patent review (2005 – present)

Novel metabotropic glutamate receptor 2/3 antagonists and their therapeutic applications: a patent review (2005 – present)

Co-operative binding assay for the characterization of mGlu4 allosteric modulators

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

Contact Info

Product

Resources

About