Advertisement

Topics

Optical Modulation of Metabotropic Glutamate Receptor Type 5 In Vivo Using a Photoactive Drug.

07:00 EST 1st January 2019 | BioPortfolio

Summary of "Optical Modulation of Metabotropic Glutamate Receptor Type 5 In Vivo Using a Photoactive Drug."

Optopharmacology is a very promising approach based on the use of light-deliverable drugs, which allows manipulating physiological processes with high spatiotemporal resolution. Light-dependent drugs (i.e. caged-compounds) targeting G protein-coupled receptors (GPCRs) have been developed to provide great pharmacological precision on the control of pain. Metabotropic glutamate type 5 (mGlu) receptors are widely expressed through the pain neuraxis and play a key role in pain transmission. In line with this, selective mGlu receptor negative allosteric modulators (NAMs) have consistently shown analgesic activity in experimental animal models of inflammatory pain. Accordingly, we synthesized a light-deliverable drug (i.e. caged compound) using the chemical structure of raseglurant, a mGlu receptor NAM, as a molecular scaffold. And thereafter, we evaluated the analgesic activity of the caged compound in formalin-injected (hind paw) mice upon light irradiation (405 nm). Of note, light was both delivered at the peripheral (i.e. hind paw) and central level (i.e. thalamus), by means of brain-implanted fiber-optics. The novel light-deliverable drug, JF-NP-26, showed antinociceptive activity upon violet light irradiation either of the hind paw or the thalamus, demonstrating the ability of precisely activating, in time and space, the caged compound. Here, we describe in detail the protocol used to perform a reliable and reproducible formalin nociception test in mice using an optopharmacology approach (i.e. light-deliverable compounds).

Affiliation

Journal Details

This article was published in the following journal.

Name: Methods in molecular biology (Clifton, N.J.)
ISSN: 1940-6029
Pages: 351-359

Links

DeepDyve research library

PubMed Articles [21070 Associated PubMed Articles listed on BioPortfolio]

The developmental expression of metabotropic glutamate receptor 4 in prenatal human frontal lobe and neurogenesis regions.

Metabotropic glutamate receptors, besides ionotropic receptors, mediate the complicated effect of glutamate on neurogenesis. Previous studies showed that metabotropic glutamate receptor 4 (mGluR4) reg...

Computationally Guided Identification of Allosteric Agonists of the Metabotropic Glutamate 7 Receptor.

The metabotropic glutamate 7 (mGlu7) receptor belongs to the group III of mGlu receptors. Since the mGlu7 receptor can control excitatory neurotransmission in the hippocampus and cortex, modulation of...

Glutamate metabotropic receptors in the lateral hypothalamus/perifornical area reduce the CO chemoreflex.

It has been shown that the lateral hypothalamus/perifornical area (LH/PFA) exerts an important role on arousal-state variations of the central chemoreflex, but the mechanisms that underlie LH/PFA chem...

Synthesis and evaluation of 4-(2-fluoro-4-Cmethoxyphenyl)-5-((2-methylpyridin-4-yl)methoxy)picolinamide for PET imaging of the metabotropic glutamate receptor 2 in the rat brain.

Metabotropic glutamate receptor 2 (mGluR2) has been suggested as a therapeutic target for treating schizophrenia-like symptoms arising from increased glutamate transmission in the human forebrain. How...

A single nucleotide polymorphism in the metabotropic glutamate receptor 7 gene is associated with multiple sclerosis in Iranian population.

Glutamate excitotoxicity has been previously associated with development of multiple sclerosis (MS). The metabotropic glutamate receptor 7 (GRM7) gene is a G protein-coupled receptor that suppresses t...

Clinical Trials [8971 Associated Clinical Trials listed on BioPortfolio]

The Safety and Efficacy of Neramexane in Patients With Moderate to Severe Alzheimer's Disease

Memory loss and difficulties with thinking associated with Alzheimer's disease may be due to chronic release of a brain chemical called glutamate. Glutamate helps transmit messages between...

A Noninterventional Genotype/Phenotype Study of mGluR Mutations in Children and Adolescents With ADHD

This noninterventional study will assess genomic changes in the metabotropic glutamate receptor (mGluR) network in children and adolescents with ADHD.

Metabotropic Glutamate Receptor-5 (mGlur5) Effects on Reward-Related fMRI-BOLD Activation in FHP and FHN

The purpose of this pilot study is to evaluate the role of Mavoglurant in clarifying the neurobiology of alcoholism risk. This is a 1-site, randomized, within subjects, counterbalanced dou...

Real Time Optical Coherence Tomography (OCT) of Human Tissue

This is a single-arm, prospective, study of an optical imaging device on approximately twenty (20) subjects undergoing lumpectomies at one study site. In vivo and ex vivo imaging will be p...

Does Subacromial Injection With Glutamate Receptor Antagonist, Ketamine, Attenuate Pain in Rotator Cuff Tendinopathy?

The hypothesis of the present study is that in patients with rotator cuff tendinopathy a specific pharmacological blocking of peripheral glutamate-receptor N-methyl-d-aspartate receptor ty...

Medical and Biotech [MESH] Definitions

A type I G protein-coupled receptor mostly expressed post-synaptic pyramidal cells of the cortex and CENTRAL NERVOUS SYSTEM.

Cell surface proteins that bind glutamate and act through G-proteins to influence second messenger systems. Several types of metabotropic glutamate receptors have been cloned. They differ in pharmacology, distribution, and mechanisms of action.

A class of ligand-gated ion channel receptors that have specificity for GLUTAMATE. They are distinct from METABOTROPIC GLUTAMATE RECEPTORS which act through a G-protein-coupled mechanism.

Cell-surface proteins that bind glutamate and trigger changes which influence the behavior of cells. Glutamate receptors include ionotropic receptors (AMPA, kainate, and N-methyl-D-aspartate receptors), which directly control ion channels, and metabotropic receptors which act through second messenger systems. Glutamate receptors are the most common mediators of fast excitatory synaptic transmission in the central nervous system. They have also been implicated in the mechanisms of memory and of many diseases.

A receptor that is specific for IGF-II and mannose-6-phosphate. The receptor is a 250-kDa single chain polypeptide which is unrelated in structure to the type 1 IGF receptor (RECEPTOR, IGF TYPE 1) and does not have a tyrosine kinase domain.

Advertisement
Quick Search
Advertisement
Advertisement

 


DeepDyve research library

Relevant Topics

Pharmacy
Pharmacy is the science and technique of preparing as well as dispensing drugs and medicines. It is a health profession that links health sciences with chemical sciences and aims to ensure the safe and effective use of pharmaceutical drugs. The scope of...

Nutrition
Within medicine, nutrition (the study of food and the effect of its components on the body) has many different roles. Appropriate nutrition can help prevent certain diseases, or treat others. In critically ill patients, artificial feeding by tubes need t...

Anesthesiology
An anesthesiologist (US English) or anaesthetist (British English) is a physician trained in anesthesia and perioperative medicine. Anesthesiologists are physicians who provide medical care to patients in a wide variety of (usually acute) situations. ...


Searches Linking to this Article