From Wikipedia, the free encyclopedia
IDRA-21 is an ampakine drug derived from aniracetam. IDRA-21 is a chiral molecule, with (+)-IDRA-21 being the active form.[1]
IDRA-21 shows nootropic effects in animal studies, significantly improving learning and memory. It is around 10-30x more potent than aniracetam in reversing cognitive deficits induced by alprazolam or scopolamine,[2][3] and produces sustained effects lasting for up to three days after a single dose.[4] The mechanism for this action is thought to be through promoting the induction of long-term potentiation between synapses in the brain.[5]
IDRA-21 does not produce neurotoxicity under normal conditions,[6] although it may worsen neuronal damage following global ischemia after stroke or seizures.[7]
In comparison to the benzoylpiperidine derived ampakine drugs, IDRA-21 was more potent than CX-516, but less potent than CX-546.[8] Newer benzothiadiazide derivatives with greatly increased potency compared to IDRA-21 have been developed,[9][10] but these have not been researched to the same extent, with the benzoylpiperidine and benzoylpyrrolidine CX- series of drugs being favoured for clinical development, most likely due to more favourable toxicity profiles at high doses.[11]
References
- ^ Uzunov, DP; Zivkovich; Pirkle; Costa; Guidotti (Aug 1995). [Expression error: Missing operand for > "Enantiomeric resolution with a new chiral stationary phase of 7-chloro-3-methyl-3,4-dihydro-2H-1,2,4-benzothiadiazine S,S-dioxide, a cognition-enhancing benzothiadiazine derivative"]. Journal of pharmaceutical sciences 84 (8): 937–42. ISSN 0022-3549. PMID 7500277.
- ^ Thompson, DM; Guidotti; Dibella; Costa (Aug 1995). [Expression error: Missing operand for > "7-Chloro-3-methyl-3,4-dihydro-2H-1,2,4-benzothiadiazine S,S-dioxide (IDRA 21), a congener of aniracetam, potently abates pharmacologically induced cognitive impairments in patas monkeys"]. Proceedings of the National Academy of Sciences of the United States of America 92 (17): 7667–71. ISSN 0027-8424. PMID 7644474.
- ^ Zivkovic, I; Thompson; Bertolino; Uzunov; Dibella; Costa; Guidotti (Jan 1995). [Expression error: Missing operand for > "7-Chloro-3-methyl-3-4-dihydro-2H-1,2,4 benzothiadiazine S,S-dioxide (IDRA 21): a benzothiadiazine derivative that enhances cognition by attenuating DL-alpha-amino-2,3-dihydro-5-methyl-3-oxo-4-isoxazolepropanoic acid (AMPA) receptor desensitization"]. The Journal of pharmacology and experimental therapeutics 272 (1): 300–9. ISSN 0022-3565. PMID 7815345.
- ^ Buccafusco, JJ; Weiser; Winter; Klinder; Terry (Jan 2004). [Expression error: Missing operand for > "The effects of IDRA 21, a positive modulator of the AMPA receptor, on delayed matching performance by young and aged rhesus monkeys"]. Neuropharmacology 46 (1): 10–22. ISSN 0028-3908. PMID 14654093.
- ^ Arai, A; Guidotti; Costa; Lynch (Sep 1996). [Expression error: Missing operand for > "Effect of the AMPA receptor modulator IDRA 21 on LTP in hippocampal slices"]. Neuroreport 7 (13): 2211–5. ISSN 0959-4965. PMID 8930991.
- ^ Impagnatiello, F; Oberto; Longone; Costa; Guidotti (Jun 1997). "7-Chloro-3-methyl-3,4-dihydro-2H-1,2,4-benzothiadiazine S,S-dioxide: a partial modulator of AMPA receptor desensitization devoid of neurotoxicity" (Free full text). Proceedings of the National Academy of Sciences of the United States of America 94 (13): 7053–8. ISSN 0027-8424. PMID 9192690. http://www.pnas.org/cgi/pmidlookup?view=long&pmid=9192690.
- ^ Yamada, KA; Covey; Hsu; Hu; Hu; He (May 1998). [Expression error: Missing operand for > "The diazoxide derivative IDRA 21 enhances ischemic hippocampal neuron injury"]. Annals of neurology 43 (5): 664–9. doi:10.1002/ana.410430517. ISSN 0364-5134. PMID 9585363.
- ^ Nagarajan, N; Quast; Boxall; Shahid; Rosenmund (Nov 2001). [Expression error: Missing operand for > "Mechanism and impact of allosteric AMPA receptor modulation by the ampakine CX546"]. Neuropharmacology 41 (6): 650–63. ISSN 0028-3908. PMID 11640919.
- ^ Phillips, D; Sonnenberg; Arai; Vaswani; Krutzik; Kleisli; Kessler; Granger et al. (May 2002). [Expression error: Missing operand for > "5'-alkyl-benzothiadiazides: a new subgroup of AMPA receptor modulators with improved affinity"]. Bioorganic & medicinal chemistry 10 (5): 1229–48. ISSN 0968-0896. PMID 11886787.
- ^ Arai, AC; Xia; Kessler; Phillips; Chamberlin; Granger; Lynch (Sep 2002). "Effects of 5'-alkyl-benzothiadiazides on (R,S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor biophysics and synaptic responses" (Free full text). Molecular pharmacology 62 (3): 566–77. ISSN 0026-895X. PMID 12181433. http://molpharm.aspetjournals.org/cgi/pmidlookup?view=long&pmid=12181433.
- ^ Black, MD (Apr 2005). [Expression error: Missing operand for > "Therapeutic potential of positive AMPA modulators and their relationship to AMPA receptor subunits. A review of preclinical data"]. Psychopharmacology 179 (1): 154–63. doi:10.1007/s00213-004-2065-6. ISSN 0033-3158. PMID 15672275.
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| Agonists: Glutamate/Acite Site Competitive Agonists: Aspartate • Glutamate • Homoquinolinic Acid • Ibotenic Acid • NMDA • Quinolinic Acid • Tetrazolylglycine; Glycine Site Agonists: ACBD • ACPC • ACPD • Alanine • CCG • Cycloserine • DHPG • Fluoroalanine • Glycine • HA-966 • L-687,414 • Milacemide • Sarcosine • Serine • Tetrazolylglycine; Polyamine Site Agonists: Acamprosate • Spermidine • SpermineAntagonists: Competitive Antagonists: AP5 (APV) • AP7 • CGP-37849 • CGP-39551 • CGP-39653 • CGP-40116 • CGS-19755 • CPP • LY-233,053 • LY-235,959 • LY-274,614 • MDL-100,453 • Midafotel (d-CPPene) • NPC-12,626 • NPC-17,742 • PBPD • PEAQX • Perzinfotel • PPDA • SDZ-220581 • Selfotel (CGS-19,755); Noncompetitive Antagonists: ARR-15,896 • Caroverine • Dexanabinol (HU-211) • FPL-12495 • FR-115,427 • Hodgkinsine • Magnesium • MDL-27,266 • NPS-1506 • Psychotridine • Zinc; Uncompetitive Pore Blockers: 2-MDP • 8A-PDHQ • Amantadine • Aptiganel (CNS-1102) • ARL-12,495 • ARL-15,896-AR • ARL-16,247 • Budipine • Delucemine • Dexoxadrol • Dieticyclidine • Dizocilpine (MK-801) • Endopsychosin • Esketamine • Etoxadrol • Eticyclidine • Gacyclidine • Ibogaine • Indantadol (CHF-3381) • Ketamine • Ketobemidone • Loperamide • Memantine • Meperidine (Pethidine) • Methadone • Methorphan ( Dextromethorphan, Levomethorphan) • Milnacipran • Morphanol ( Dextrorphan, Levorphanol) • NEFA • Neramexane • Nitrous Oxide • Noribogaine • Orphenadrine • Phencyclamine • Phencyclidine • Propoxyphene • Remacemide • Rhynchophylline • Riluzole • Rimantadine • Rolicyclidine • Tenocyclidine • Tiletamine • Tramadol • Xenon; Glycine Site Antagonists: ACEA-1021 • ACEA-1328 • ACPC • Carisoprodol • CGP-39653 • CKA • DCKA • Felbamate • Gavestinel (GV-150,526) • GV-196,771 • Kynurenic Acid • L-689,560 • L-701,324 • Lacosamide • Licostinel (ACEA-1021) • LU-73,068 • MDL-105,519 • Meprobamate • MRZ 2/576 • PNQX • ZD-9379; NR2B Subunit Antagonists: Besonprodil • CO-101,244 (PD-174,494) • CP-101,606 • Eliprodil • Haloperidol • Ifenprodil • Isoxsuprine • Nylidrin • Ro8-4304 • Ro25-6981 • Traxoprodil; Polyamine Site Antagonists: Arcaine • Co 101676 • Diaminopropane • Diethylenetriamine • Huperzine A • Putrescine • Ro 25-6981; Unclassified/Unsorted Antagonists: Chloroform • Diethyl Ether • Enflurane • Ethanol (Alcohol) • Halothane • Isoflurane • Methoxyflurane | |
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| Agonists: Unselective: L-AP4; mGlu4-Selective: PHCCC • VU-001,171 • VU-0155,041; mGlu7-Selective: AMN082; mGlu8-Selective: DCPGAntagonists: Unselective: CPPG • MAP4 • MSOP • MPPG • MTPG • UBP-1112; mGlu7-Selective: MMPIP |
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