HA-966

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]

HA-966
Identifiers
IUPAC name
  • 3-Amino-1-hydroxy-pyrrolidin-2-one
CAS Number
PubChem CID
ChemSpider
UNII
CompTox Dashboard (EPA)
ECHA InfoCard100.162.446
Chemical and physical data
FormulaC4H8N2O2
Molar mass116.120 g·mol−1
3D model (JSmol)
SMILES
  • O=C1C(CCN1O)N
InChI
  • InChI=1S/C4H8N2O2/c5-3-1-2-6(8)4(3)7/h3,8H,1-2,5H2
  • Key:HCKUBNLZMKAEIN-UHFFFAOYSA-N

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]

See also

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. doi:10.1016/0304-3940(91)90069-6. PMID 1838797. S2CID 36483282.
  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. doi:10.1016/0014-2999(92)90120-S. PMID 1355434.
  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. doi:10.1016/0014-2999(92)90067-E. PMID 1313371.
  4. 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". British Journal of Pharmacology. 43 (3): 514–35. doi:10.1111/j.1476-5381.1971.tb07182.x. PMC 1665789. PMID 5157720.
  5. 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. Bibcode:1990PNAS...87..347S. doi:10.1073/pnas.87.1.347. PMC 53260. PMID 2153294.
  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. doi:10.1016/0014-2999(90)94069-A. PMID 2149338.
  7. 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. PMID 9353390.
This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.