World Library  
Flag as Inappropriate
Email this Article

Ha-966

Article Id: WHEBN0036399227
Reproduction Date:

Title: Ha-966  
Author: World Heritage Encyclopedia
Language: English
Subject: MMPIP, LY-344,545, EGLU, PEAQX, Tetrazolylglycine
Collection:
Publisher: World Heritage Encyclopedia
Publication
Date:
 

Ha-966

HA-966
Systematic (IUPAC) name
3-Amino-1-hydroxy-pyrrolidin-2-one
Clinical data
Legal status
?
Identifiers
CAS number
ATC code ?
PubChem
ChemSpider
Chemical data
Formula C4H8N2O2 
Mol. mass 116.11972 g/mol

HA-966 or (±) 3-Amino-1-hydroxy-pyrrolidin-2-one is a molecule used in scientific research as a glycine receptor and NMDA receptor antagonist / low efficacy partial agonist. It has neuroprotective and anticonvulsant,[1] anxiolytic,[2] antinociceptive[3] and sedative / hypnotic[4] effects in animal models. Pilot human clinical trials in the early 1960s showed that HA-966 appeared to benefit patients with tremors of extrapyramidal origin.[4]

The two enantiomers of HA-966 have differing pharmacological activity. The glycine/N-methyl-D-aspartate receptor antagonist activity is specific to the R-(+) enantiomer, whereas the sedative and ataxic effects are specific to the S-(-) enantiomer.[5]

R-(+)-HA-966 did not induce drug-appropriate responding in animals trained to discriminate phencyclidine (PCP) from saline, suggesting that the glycine receptor ligand R-(+)-HA-966 has a significantly different behavioral profile than drugs affecting the ion channel of the NMDA receptor complex.[6]

S-(-)-HA-966 has been described as a "γ-hydroxybutyric acid (GHB)-like agent"[7] and a "potent y-butyrolactone-like sedative",[5] but it shows no affinity for the GABAB receptor (GABABR).[7]

References

  1. ^ Vartanian MG, Taylor CP. (Nov 1991). "Different stereoselectivity of the enantiomers of HA-966 (3-amino-1-hydroxy-2-pyrrolidinone) for neuroprotective and anticonvulsant actions in vivo.". Neuroscience Letters 133 (1): 109–12.  
  2. ^ Dunn RW, Flanagan DM, Martin LL, Kerman LL, Woods AT, Camacho F, Wilmot CA, Cornfeldt ML, Effland RC, Wood PL, et al. (Apr 1992). "Stereoselective R-(+) enantiomer of HA-966 displays anxiolytic effects in rodents.". European Journal of Pharmacology 214 (2-3): 207–14.  
  3. ^ Näsström J, Karlsson U, Post C. (Feb 1992). "Antinociceptive actions of different classes of excitatory amino acid receptor antagonists in mice.". European Journal of Pharmacology 212 (1): 21–9.  
  4. ^ a b Bonta IL, De Vos CJ, Grijsen H, Hillen FC, Noach EL, Sim AW. (Nov 1971). "1-Hydroxy-3-amino-pyrrolidone-2(HA-966): a new GABA-like compound, with potential use in extrapyramidal diseases.".  
  5. ^ a b Singh L, Donald AE, Foster AC, Hutson PH, Iversen LL, Iversen SD, Kemp JA, Leeson PD, Marshall GR, Oles RJ, et al. (Jan 1990). "Enantiomers of HA-966 (3-amino-1-hydroxypyrrolid-2-one) exhibit distinct central nervous system effects: (+)-HA-966 is a selective glycine/N-methyl-D-aspartate receptor antagonist, but (-)-HA-966 is a potent gamma-butyrolactone-like sedative.". Proc Natl Acad Sci USA. 87 (1): 347–51.  
  6. ^ Singh L, Menzies R, Tricklebank MD. (Sep 1990). "The discriminative stimulus properties of (+)-HA-966, an antagonist at the glycine/N-methyl-D-aspartate receptor.". European Journal of Pharmacology. 186 (1): 129–32.  
  7. ^ a b Morrow BA, Lee EJ, Taylor JR, Elsworth JD, Nye HE, Roth RH. (Nov 1997). "(S)-(-)-HA-966, a gamma-hydroxybutyrate-like agent, prevents enhanced mesocorticolimbic dopamine metabolism and behavioral correlates of restraint stress, conditioned fear and cocaine sensitization.". J Pharmacol Exp Ther. 283 (2): 712–21.  
This article was sourced from Creative Commons Attribution-ShareAlike License; additional terms may apply. World Heritage Encyclopedia content is assembled from numerous content providers, Open Access Publishing, and in compliance with The Fair Access to Science and Technology Research Act (FASTR), Wikimedia Foundation, Inc., Public Library of Science, The Encyclopedia of Life, Open Book Publishers (OBP), PubMed, U.S. National Library of Medicine, National Center for Biotechnology Information, U.S. National Library of Medicine, National Institutes of Health (NIH), U.S. Department of Health & Human Services, and USA.gov, which sources content from all federal, state, local, tribal, and territorial government publication portals (.gov, .mil, .edu). Funding for USA.gov and content contributors is made possible from the U.S. Congress, E-Government Act of 2002.
 
Crowd sourced content that is contributed to World Heritage Encyclopedia is peer reviewed and edited by our editorial staff to ensure quality scholarly research articles.
 
By using this site, you agree to the Terms of Use and Privacy Policy. World Heritage Encyclopedia™ is a registered trademark of the World Public Library Association, a non-profit organization.
 


Copyright © World Library Foundation. All rights reserved. eBooks from Project Gutenberg are sponsored by the World Library Foundation,
a 501c(4) Member's Support Non-Profit Organization, and is NOT affiliated with any governmental agency or department.