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Editor-in-Chief: Natalia Ortúzar
Impact Factor: 2.968
ISI Journal Citation Reports © Ranking: 2014: 19/59 (Chemistry Medicinal); 83/255 (Pharmacology & Pharmacy)
Online ISSN: 1860-7187
August 03, 2010
VIP: Novel 3-Carboxy- and 3-Phosphonopyrazoline Amino Acids as Potent and Selective NMDA Receptor Antagonists: Design, Synthesis, and Pharmacological Characterization
Paola Conti,* Andrea Pinto, Lucia Tamborini, Ulf Madsen, Birgitte Nielsen, Hans Bräuner-Osborne, Kasper B. Hansen, Elisa Landucci, Domenico E. Pellegrini-Giampietro, Giovambattista De Sarro, Eugenio Donato Di Paola, and Carlo De Micheli
As the most abundant neurotransmitter in the human central nervous system, L-glutamate plays a central role in a wide range of neurological processes. The N-methyl-D-aspartic acid (NMDA) receptor is one of several glutamate-activated receptors; over-activation of this receptor leads to an unchecked Ca2+ influx, which has been associated with brain and spinal cord injuries, epilepsy, and Alzheimer's disease, to name just a few. Therefore, compounds that can specifically antagonize the NMDA receptor have the potential to treat a significant number of neurological disorders.
This paper by Conti et al. describes the design and synthesis of new NMDA receptor antagonists that target the glutamate binding site. The authors undertook pharmacological characterization at various types and subtypes of glutamate receptors, and among the derivatives tested, two stood out for their promising in vitro and in vivo activity as neuroprotective and anticonvulsant agents.
Received April 30, 2010; published online July 27, 2010, DOI: 10.1002/cmdc.201000184.