| 词条 | HA-966 |
| 释义 |
| Watchedfields = | verifiedrevid = | IUPAC_name = 3-Amino-1-hydroxy-pyrrolidin-2-one | image = Molecular_Structure_of_HA-966.png | width = 200 | tradename = | pregnancy_AU = | pregnancy_US = | pregnancy_category = | legal_AU = | legal_CA = | legal_UK = | legal_US = | legal_status = | routes_of_administration = | bioavailability = | protein_bound = | metabolism = | elimination_half-life = | excretion = | CAS_number = 1003-51-6 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = F2JLV9220T | ATC_prefix = | ATC_suffix = | PubChem = 1232 | IUPHAR_ligand = | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank = | ChemSpiderID = 1195 | StdInChI = 1S/C4H8N2O2/c5-3-1-2-6(8)4(3)7/h3,8H,1-2,5H2 | StdInChIKey = HCKUBNLZMKAEIN-UHFFFAOYSA-N | C=4 | H=8 | N=2 | O=2 | molecular_weight = 116.11972 g/mol | smiles = O=C1C(CCN1O)N }}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
References1. ^{{cite journal |vauthors=Vartanian MG, Taylor CP |title=Different stereoselectivity of the enantiomers of HA-966 (3-amino-1-hydroxy-2-pyrrolidinone) for neuroprotective and anticonvulsant actions in vivo. |journal=Neuroscience Letters |volume=133 |issue=1 |pages=109–12 |date=Nov 1991 |pmid=1838797 |doi=10.1016/0304-3940(91)90069-6 |url=}} {{Ionotropic glutamate receptor modulators}}2. ^{{cite journal |vauthors=Dunn RW, Flanagan DM, Martin LL, Kerman LL, Woods AT, Camacho F, Wilmot CA, Cornfeldt ML, Effland RC, Wood PL |title=Stereoselective R-(+) enantiomer of HA-966 displays anxiolytic effects in rodents. |journal=European Journal of Pharmacology |volume=214 |issue=2–3 |pages=207–14 |date=Apr 1992 |pmid=1355434 |doi=10.1016/0014-2999(92)90120-S |url=|display-authors=etal}} 3. ^{{cite journal |vauthors=Näsström J, Karlsson U, Post C |title=Antinociceptive actions of different classes of excitatory amino acid receptor antagonists in mice. |journal=European Journal of Pharmacology |volume=212 |issue=1 |pages=21–9 |date=Feb 1992 |pmid=1313371 |doi=10.1016/0014-2999(92)90067-E |url=}} 4. ^1 {{cite journal |vauthors=Bonta IL, De Vos CJ, Grijsen H, Hillen FC, Noach EL, Sim AW |title=1-Hydroxy-3-amino-pyrrolidone-2(HA-966): a new GABA-like compound, with potential use in extrapyramidal diseases. |journal=British Journal of Pharmacology |volume=43 |issue=3 |pages=514–35 |date=Nov 1971 |pmid=5157720 |doi= 10.1111/j.1476-5381.1971.tb07182.x|pmc=1665789}} 5. ^1 {{cite journal |vauthors=Singh L, Donald AE, Foster AC, Hutson PH, Iversen LL, Iversen SD, Kemp JA, Leeson PD, Marshall GR, Oles RJ |title=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. |journal=Proc Natl Acad Sci USA |volume=87 |issue=1 |pages=347–51 |date=Jan 1990 |pmid=2153294 |doi= 10.1073/pnas.87.1.347|pmc=53260|display-authors=etal}} 6. ^{{cite journal |vauthors=Singh L, Menzies R, Tricklebank MD |title=The discriminative stimulus properties of (+)-HA-966, an antagonist at the glycine/N-methyl-D-aspartate receptor. |journal=European Journal of Pharmacology |volume=186 |issue=1 |pages=129–32 |date=Sep 1990 |pmid=2149338 |doi=10.1016/0014-2999(90)94069-A |url= }} 7. ^1 {{cite journal |vauthors=Morrow BA, Lee EJ, Taylor JR, Elsworth JD, Nye HE, Roth RH |title=(S)-(−)-HA-966, a gamma-hydroxybutyrate-like agent, prevents enhanced mesocorticolimbic dopamine metabolism and behavioral correlates of restraint stress, conditioned fear and cocaine sensitization. |journal=J Pharmacol Exp Ther |volume=283 |issue=2 |pages=712–21 |date=Nov 1997 |pmid=9353390 |doi= |url=http://jpet.aspetjournals.org/content/283/2/712.full.pdf+html}} 4 : Amines|Ketones|NMDA receptor antagonists|Pyrrolidines |
| 随便看 |
|
开放百科全书收录14589846条英语、德语、日语等多语种百科知识，基本涵盖了大多数领域的百科知识，是一部内容自由、开放的电子版国际百科全书。