A new metabotropic glutamate receptor agonist with in vivo anti-allodynic activity

• Main Authors: Stanley, N.J., Hutchinson, M.R., Kvist, T., Nielsen, B., Mathiesen, J.M., Brauner-Osborne, H., Avery, T.D., Tiekink, E.R.T., Pedersen, D.S., Irvine, R., Abell, A.D., Taylor, D.K.
• Format: Article
• Published: Elsevier 2010
• Subjects: Q Science (General)
• Online Access: http://eprints.um.edu.my/12517/

As part of the vital search towards improved therapeutic agents for the treatment of neuropathic pain, the central nervous system glutamate receptors have become a major focus of research. Outlined herein are the syntheses of two new biologically active 3'-cycloalkyl-substituted carboxycyclopropylglycines, utilizing novel synthetic chemistry. The reaction between substituted 1,2-dioxines and an aminophosphonate furnished the cyclopropane core in a single step with all required stereochemistry of pendant groups. In vitro binding assays at metabotropic glutamate receptors revealed selective activity. In vivo testing in a rodent model of neuropathic pain indicated one amino acid significantly and dose-dependently decreased mechanical allodynia. (C) 2010 Elsevier Ltd. All rights reserved.