Novel Fluorine-Containing NMDA Antagonists for Brain Imaging: In Vitro Evaluation
Abstract
The NMDA receptor has been implicated in neuronal death following stroke, brain injury and neurodegenerative disorders (e.g. Alzheimer's, Parkinson's and Huntington's disease) and in physiological functions (e.g. memory and cognition). Non-competitive antagonists, such as MK- 801 and CNS-1102, that block the action of glutamate at the NMDA receptor have been shown to be neuroprotective by blocking the influx of calcium into the cells. As a result, they are being considered as therapeutic agents for the above mentioned diseases. Several Fluorine-containing novel analogs of NMDA channel blockers have been synthesized and evaluated in search of a compound suitable for 18F labeling and Positron Emission Tomography (PET). Based on in vitro binding assay studies on rat brain membranes, the novel compounds examined displayed a range of affinities. Preliminary analyses indicated that chlorine is the best halogen on the ring, and that ethyl fluoro derivatives are more potent than methyl-fluoro compounds. Further analysis based on autoradiography will be needed to examine the regional binding characteristics of the novel compounds examined in this study. Labeling with 18F will allow the use of these compounds in humans, generating new insights into mechanisms and treatment of diseases involving malfunction of the glutamatergic system in the brain.
- Authors:
- Publication Date:
- Research Org.:
- DOESC (USDOE Office of Science (SC) (United States))
- Sponsoring Org.:
- USDOE Office of Science (SC)
- OSTI Identifier:
- 1051241
- Resource Type:
- Journal Article
- Journal Name:
- Journal of Undergraduate Research
- Additional Journal Information:
- Journal Volume: 1
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS; AUTORADIOGRAPHY; BRAIN; CALCIUM; CHLORINE; DEATH; DISEASES; DRUGS; EVALUATION; HALOGENS; IN VITRO; MEMBRANES; POSITRONS; TOMOGRAPHY
Citation Formats
Alvarado, M, and Biegon, A. Novel Fluorine-Containing NMDA Antagonists for Brain Imaging: In Vitro Evaluation. United States: N. p., 2001.
Web.
Alvarado, M, & Biegon, A. Novel Fluorine-Containing NMDA Antagonists for Brain Imaging: In Vitro Evaluation. United States.
Alvarado, M, and Biegon, A. 2001.
"Novel Fluorine-Containing NMDA Antagonists for Brain Imaging: In Vitro Evaluation". United States. https://www.osti.gov/servlets/purl/1051241.
@article{osti_1051241,
title = {Novel Fluorine-Containing NMDA Antagonists for Brain Imaging: In Vitro Evaluation},
author = {Alvarado, M and Biegon, A},
abstractNote = {The NMDA receptor has been implicated in neuronal death following stroke, brain injury and neurodegenerative disorders (e.g. Alzheimer's, Parkinson's and Huntington's disease) and in physiological functions (e.g. memory and cognition). Non-competitive antagonists, such as MK- 801 and CNS-1102, that block the action of glutamate at the NMDA receptor have been shown to be neuroprotective by blocking the influx of calcium into the cells. As a result, they are being considered as therapeutic agents for the above mentioned diseases. Several Fluorine-containing novel analogs of NMDA channel blockers have been synthesized and evaluated in search of a compound suitable for 18F labeling and Positron Emission Tomography (PET). Based on in vitro binding assay studies on rat brain membranes, the novel compounds examined displayed a range of affinities. Preliminary analyses indicated that chlorine is the best halogen on the ring, and that ethyl fluoro derivatives are more potent than methyl-fluoro compounds. Further analysis based on autoradiography will be needed to examine the regional binding characteristics of the novel compounds examined in this study. Labeling with 18F will allow the use of these compounds in humans, generating new insights into mechanisms and treatment of diseases involving malfunction of the glutamatergic system in the brain.},
doi = {},
url = {https://www.osti.gov/biblio/1051241},
journal = {Journal of Undergraduate Research},
number = ,
volume = 1,
place = {United States},
year = {Mon Jan 01 00:00:00 EST 2001},
month = {Mon Jan 01 00:00:00 EST 2001}
}