+ Site Statistics
References:
52,654,530
Abstracts:
29,560,856
PMIDs:
28,072,755
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

Trialkylglycines: a new family of compounds with in vivo neuroprotective activity



Trialkylglycines: a new family of compounds with in vivo neuroprotective activity



Cns Drug Reviews 9(3): 263-274



Glutamate neurotoxicity is involved in the pathogenesis of neurodegenerative disorders such as Huntington's, Parkinson's and Alzheimer's diseases. It plays also a major role in the neuronal damage that occurs in brain ischemia and head trauma. Finding molecules that prevent or reverse glutamate neurotoxicity (excitotoxicity) is, therefore, of great interest. Strategies aimed at this end include the screening of libraries of compounds synthesized by combinatorial chemistry to find molecules that prevent neuronal death in vitro and in vivo. A library of trialkylglycines was screened to assess whether they prevent glutamate-induced neuronal death in primary cultures of cerebellar neurons. Two types of trialkylglycines have been found that significantly reduce the incidence of glutamate-induced neuronal death. The first type includes two compounds (referred to as 6-1-2 and 6-1-10) that efficiently prevent glutamate or NMDA-induced neuronal death. They also prevent excitotoxicity in vivo as assessed by using two animal models of excitotoxicity: acute intoxication with ammonia and a model of cerebral ischemia in rats. Trialkylglycines 6-1-2 and 6-1-10 prevent ammonia-induced (NMDA receptor-mediated) death of mice and neuronal degeneration in the model of cerebral ischemia. The trialkylglycines of the second type act as open channel blockers of the NMDA receptor. The first group of trialkylglycines does not block NMDA receptor channels and does not affect the glutamate-nitric oxide-cGMP pathway. Their molecular target has not yet been identified. These two types of trialkylglycines (especially those that do not affect NMDA receptor function) might represent effective drugs for the treatment of neurodegeneration. They are likely to be well tolerated and have fewer side effects than NMDA receptor antagonists.

(PDF emailed within 0-6 h: $19.90)

Accession: 035985909

Download citation: RISBibTeXText

PMID: 14530798

DOI: 10.1111/j.1527-3458.2003.tb00253.x


Related references

Prevention of in vivo excitotoxicity by a family of trialkylglycines, a novel class of neuroprotectants. Journal of Pharmacology and Experimental Therapeutics 301(1): 29-36, 2002

Identification of trialkylglycines-based blockers of the NMDA receptor with in vitro and in vivo neuroprotectant activity against excitotoxicity. Society for Neuroscience Abstracts 27(1): 272, 2001

Synthesis and biological evaluation of non-peptidic cyclophilin binding compounds and their in vivo neuroprotective effects. Abstracts of Papers American Chemical Society 224(1-2): MEDI 267, 2002

Two new compounds from Atractylodes macrocephala with neuroprotective activity. Journal of Asian Natural Products Research 19(1): 35-41, 2017

A new family of DNA targeting compounds have potent activity against vancomycin resistant Enterococci and methicillin resistant Staphylococcus aureus Demonstration of efficacy in vivo. Abstracts of the Interscience Conference on Antimicrobial Agents & Chemotherapy 42: 200, 2002

Neuroprotective or neurotoxic activity of 1-methyl-1,2,3,4-tetrahydroisoquinoline and related compounds. Bioorganic & Medicinal Chemistry Letters 13(17): 2853-2855, 1 September, 2003

Creatinyl amino acids: new hybrid compounds with neuroprotective activity. Journal of Peptide Science 17(9): 620-626, 2011

Compounds with neuroprotective activity from the medicinal plant Machilus thunbergii. Journal of Enzyme Inhibition and Medicinal Chemistry 24(5): 1117-1121, 2010

Synthesis and in vitro, ex-vivo and in vivo activity of hybrid compounds linking a potent ROS and RNS scavenger activity with diverse substrates addressed to pass across the blood-brain barrier. European Journal of Medicinal Chemistry 123: 788-802, 2017

Neuroprotective and antioxidant activity of compounds from the aerial parts of Dioscorea opposita. Journal of Natural Products 68(8): 1259-1261, 2005

In vivo Neuroprotective Activity of Epopeptide AB Against Ischemic Damage. Cytotechnology 47(1-3): 139-144, 2008

Latanoprost exerts neuroprotective activity in vitro and in vivo. Experimental Eye Research 72(4): 479-486, 2001

Novel glycineB antagonists show neuroprotective activity in vivo. Amino Acids 14(1-3): 223-226, 1999

Conjugation of catechins with cysteine generates antioxidant compounds with enhanced neuroprotective activity. Phytochemistry 66(17): 2032-2037, 2005

Neuroprotective activity and cytotoxic potential of two Parmeliaceae lichens: Identification of active compounds. Phytomedicine 22(9): 847-855, 2015