Neuroprotection and neuroegenisis by administering cyclic prolyl glycine

Patent Number: 7,232,798

This invention relates to the discovery of the functions of cyclic Propyl Glycine as a novel antagonist that either blocks the AMPA and/or the NMDA receptors. Since agonism of these receptors is associated with excitotoxic neuronal death, the invention covers the use of cyclic propyl glycine as a neuroprotectant in a variety of settings including stroke and neurodegenerative diseases.

The patent claims the use of cyclic propyl glycine alone, or as an adjuvant to neuroprotective agents known in the art such as: insulin-like growth factor-I (IGF-I), insulin growth-like factor-II (IGF-II), transforming growth factor-.beta.1, activin, growth hormone, nerve growth factor, growth hormone binding protein, IGF-binding proteins (especially IGFBP-), basic fibroblast growth factor, acidic fibroblast growth factor, the hst/Kfgk gene product, fibroblast growth factor 3 (FGF-3), fibroblast growth factor 4 (FGF-4), fibroblast growth factor 6 (FGF-6), keratinocyte growth factor, androgen-induced growth factor, int-2, fibroblast growth factor homologous factor-1 (FHF-1), fibroblast growth factor homologous factor-2 (FHF-2), fibroblast growth factor homologous factor-3 (FHF-3), fibroblast growth factor homologous factor-4 (FHF-4), karatinocyte growth factor 2, glial-activating factor, fibroblast growth factor-10 (FGF-10) and fibroblast growth factor-16 (FGF-16), ciliary neurotrophic factor, brain derived growth factor, neurotrophin 3, neurotrophin 4, bone morphogenetic protein 2 (BMP-2), glial-cell line derived neurotrophic factor, activity-dependant neurotrophic factor, cytokine leukemia, inhibiting factor, oncostatin M, interleukin, .beta., .alpha., .chi., or consensus interferon, tumor necrosis factor-.alpha. (TNF-.alpha.), clomethiazole; kynurenic acid, Semax, FK506 (tacrolimus), L-threo-1-pheyl-2-decanoylamino-3-morpholino-1-propanol, andrenocorticotropin-(4-9_analogue (ORG 2766)) and dizolcipine (MK-801), and selegiline; or b) said neuroprotective agent is a glutamate antagonist selected from the group consisting of NPS1506, GV1505260, MK-801, and GV150526; or c) said neuroprotective agent is an alpha-amino-3-hydroxy-5-methyl 4-isoxazole proprionic acid (AMPA) antagonist selected from the group consisting of 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(f)-quinoxaline (NBQX), LY303070 and LY300164; or d) said neuroprotective agent is an anti-inflammatory agent directed against mucosal vascular addressing cell adhesion molecular 1 (MAdCAM-1) and/or integrin .alpha.4 receptors.

View this patent on the USPTO website.