HA-966
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ECHA InfoCard | 100.162.446 |
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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
References
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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". British Journal of Pharmacology. 43 (3): 514–35. doi:10.1111/j.1476-5381.1971.tb07182.x. PMC 1665789. PMID 5157720.
- ^ 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. Bibcode:1990PNAS...87..347S. doi:10.1073/pnas.87.1.347. PMC 53260. PMID 2153294.
- ^ 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.
- ^ 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. PMID 9353390.
- v
- t
- e
- Agonists: Main site agonists: 5-Fluorowillardiine
- Acromelic acid (acromelate)
- AMPA
- BOAA
- Domoic acid
- Glutamate
- Ibotenic acid
- Proline
- Quisqualic acid
- Willardiine; Positive allosteric modulators: Aniracetam
- Cyclothiazide
- CX-516
- CX-546
- CX-614
- Farampator (CX-691, ORG-24448)
- CX-717
- CX-1739
- CX-1942
- Diazoxide
- Hydrochlorothiazide (HCTZ)
- IDRA-21
- LY-392098
- LY-395153
- LY-404187
- LY-451646
- LY-503430
- Mibampator (LY-451395)
- Nooglutyl
- ORG-26576
- Oxiracetam
- PEPA
- Pesampator (BIIB-104, PF-04958242)
- Piracetam
- Pramiracetam
- S-18986
- Tulrampator (S-47445, CX-1632)
- Antagonists: ACEA-1011
- ATPO
- Becampanel
- Caroverine
- CNQX
- Dasolampanel
- DNQX
- Fanapanel (MPQX)
- GAMS
- Kaitocephalin
- Kynurenic acid
- Kynurenine
- Licostinel (ACEA-1021)
- NBQX
- PNQX
- Selurampanel
- Tezampanel
- Theanine
- Topiramate
- YM90K
- Zonampanel; Negative allosteric modulators: Barbiturates (e.g., pentobarbital, sodium thiopental)
- Cyclopropane
- Enflurane
- Ethanol (alcohol)
- Evans blue
- GYKI-52466
- GYKI-53655
- Halothane
- Irampanel
- Isoflurane
- Perampanel
- Pregnenolone sulfate
- Sevoflurane
- Talampanel; Unknown/unsorted antagonists: Minocycline
- Agonists: Main site agonists: 5-Bromowillardiine
- 5-Iodowillardiine
- Acromelic acid (acromelate)
- AMPA
- ATPA
- Domoic acid
- Glutamate
- Ibotenic acid
- Kainic acid
- LY-339434
- Proline
- Quisqualic acid
- SYM-2081; Positive allosteric modulators: Cyclothiazide
- Diazoxide
- Enflurane
- Halothane
- Isoflurane
- Antagonists: ACEA-1011
- CNQX
- Dasolampanel
- DNQX
- GAMS
- Kaitocephalin
- Kynurenic acid
- Licostinel (ACEA-1021)
- LY-382884
- NBQX
- NS102
- Selurampanel
- Tezampanel
- Theanine
- Topiramate
- UBP-302; Negative allosteric modulators: Barbiturates (e.g., pentobarbital, sodium thiopental)
- Enflurane
- Ethanol (alcohol)
- Evans blue
- NS-3763
- Pregnenolone sulfate
- Agonists: Main site agonists: AMAA
- Aspartate
- Glutamate
- Homocysteic acid (L-HCA)
- Homoquinolinic acid
- Ibotenic acid
- NMDA
- Proline
- Quinolinic acid
- Tetrazolylglycine
- Theanine; Glycine site agonists: β-Fluoro-D-alanine
- ACBD
- ACC (ACPC)
- ACPD
- AK-51
- Apimostinel (NRX-1074)
- B6B21
- CCG
- D-Alanine
- D-Cycloserine
- D-Serine
- DHPG
- Dimethylglycine
- Glycine
- HA-966
- L-687414
- L-Alanine
- L-Serine
- Milacemide
- Neboglamine (nebostinel)
- Rapastinel (GLYX-13)
- Sarcosine; Polyamine site agonists: Neomycin
- Spermidine
- Spermine; Other positive allosteric modulators: 24S-Hydroxycholesterol
- DHEATooltip Dehydroepiandrosterone (prasterone)
- DHEA sulfate (prasterone sulfate)
- Epipregnanolone sulfate
- Plazinemdor
- Pregnenolone sulfate
- SAGE-201
- SAGE-301
- SAGE-718
- Antagonists: Competitive antagonists: AP5 (APV)
- AP7
- CGP-37849
- CGP-39551
- CGP-39653
- CGP-40116
- CGS-19755
- CPP
- Kaitocephalin
- LY-233053
- LY-235959
- LY-274614
- MDL-100453
- Midafotel (d-CPPene)
- NPC-12626
- NPC-17742
- PBPD
- PEAQX
- Perzinfotel
- PPDA
- SDZ-220581
- Selfotel; Glycine site antagonists: 4-Cl-KYN (AV-101)
- 5,7-DCKA
- 7-CKA
- ACC
- ACEA-1011
- ACEA-1328
- Apimostinel (NRX-1074)
- AV-101
- Carisoprodol
- CGP-39653
- CNQX
- D-Cycloserine
- DNQX
- Felbamate
- Gavestinel
- GV-196771
- Harkoseride
- Kynurenic acid
- Kynurenine
- L-689560
- L-701324
- Licostinel (ACEA-1021)
- LU-73068
- MDL-105519
- Meprobamate
- MRZ 2/576
- PNQX
- Rapastinel (GLYX-13)
- ZD-9379; Polyamine site antagonists: Arcaine
- Co 101676
- Diaminopropane
- Diethylenetriamine
- Huperzine A
- Putrescine; Uncompetitive pore blockers (mostly dizocilpine site): 2-MDP
- 3-HO-PCP
- 3-MeO-PCE
- 3-MeO-PCMo
- 3-MeO-PCP
- 4-MeO-PCP
- 8A-PDHQ
- 18-MC
- α-Endopsychosin
- Alaproclate
- Alazocine (SKF-10047)
- Amantadine
- Aptiganel
- Argiotoxin-636
- Arketamine
- ARL-12495
- ARL-15896-AR
- ARL-16247
- Budipine
- Coronaridine
- Delucemine (NPS-1506)
- Dexoxadrol
- Dextrallorphan
- Dextromethadone
- Dextromethorphan
- Dextrorphan
- Dieticyclidine
- Diphenidine
- Dizocilpine
- Ephenidine
- Esketamine
- Etoxadrol
- Eticyclidine
- Fluorolintane
- Gacyclidine
- Ibogaine
- Ibogamine
- Indantadol
- Ketamine
- Ketobemidone
- Lanicemine
- Levomethadone
- Levomethorphan
- Levomilnacipran
- Levorphanol
- Loperamide
- Memantine
- Methadone
- Methorphan
- Methoxetamine
- Methoxphenidine
- Milnacipran
- Morphanol
- NEFA
- Neramexane
- Nitromemantine
- Noribogaine
- Norketamine
- Orphenadrine
- PCPr
- PD-137889
- Pethidine (meperidine)
- Phencyclamine
- Phencyclidine
- Propoxyphene
- Remacemide
- Rhynchophylline
- Rimantadine
- Rolicyclidine
- Sabeluzole
- Tabernanthine
- Tenocyclidine
- Tiletamine
- Tramadol; Ifenprodil (NR2B) site antagonists:
- Besonprodil
- Buphenine (nylidrin)
- CO-101244 (PD-174494)
- Eliprodil
- Haloperidol
- Isoxsuprine
- Radiprodil (RGH-896)
- Rislenemdaz (CERC-301, MK-0657)
- Ro 8-4304
- Ro 25-6981
- Safaprodil
- Traxoprodil (CP-101606); NR2A-selective antagonists: MPX-004
- MPX-007
- TCN-201
- TCN-213; Cations: Hydrogen
- Magnesium
- Zinc; Alcohols/volatile anesthetics/related: Benzene
- Butane
- Chloroform
- Cyclopropane
- Desflurane
- Diethyl ether
- Enflurane
- Ethanol (alcohol)
- Halothane
- Hexanol
- Isoflurane
- Methoxyflurane
- Nitrous oxide
- Octanol
- Sevoflurane
- Toluene
- Trichloroethane
- Trichloroethanol
- Trichloroethylene
- Urethane
- Xenon
- Xylene; Unknown/unsorted antagonists: ARR-15896
- Bumetanide
- Caroverine
- Conantokin
- D-αAA
- Dexanabinol
- Flufenamic acid
- Flupirtine
- FPL-12495
- FR-115427
- Furosemide
- Hodgkinsine
- Ipenoxazone (MLV-6976)
- MDL-27266
- Metaphit
- Minocycline
- MPEP
- Niflumic acid
- Pentamidine
- Pentamidine isethionate
- Piretanide
- Psychotridine
- Transcrocetin (saffron)
- Unsorted: Allosteric modulators: AGN-241751
- See also: Receptor/signaling modulators
- Metabotropic glutamate receptor modulators
- Glutamate metabolism/transport modulators