Chemistry:HA-966
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| Formula | C4H8N2O2 |
| Molar mass | 116.120 g·mol−1 |
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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]
See also
- Rapastinel
- NRX-1074
References
- ↑ "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. Nov 1991. doi:10.1016/0304-3940(91)90069-6. PMID 1838797.
- ↑ "Stereoselective R-(+) enantiomer of HA-966 displays anxiolytic effects in rodents.". European Journal of Pharmacology 214 (2–3): 207–14. Apr 1992. doi:10.1016/0014-2999(92)90120-S. PMID 1355434.
- ↑ "Antinociceptive actions of different classes of excitatory amino acid receptor antagonists in mice.". European Journal of Pharmacology 212 (1): 21–9. Feb 1992. doi:10.1016/0014-2999(92)90067-E. PMID 1313371.
- ↑ 4.0 4.1 "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. Nov 1971. doi:10.1111/j.1476-5381.1971.tb07182.x. PMID 5157720.
- ↑ 5.0 5.1 "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. Jan 1990. doi:10.1073/pnas.87.1.347. PMID 2153294. Bibcode: 1990PNAS...87..347S.
- ↑ "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. Sep 1990. doi:10.1016/0014-2999(90)94069-A. PMID 2149338.
- ↑ 7.0 7.1 "(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. Nov 1997. PMID 9353390. http://jpet.aspetjournals.org/content/283/2/712.full.pdf+html.
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