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IDRA-21: Wikis


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Systematic (IUPAC) name
7-chloro-3-methyl-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide
CAS number 22503-72-6
ATC code  ?
PubChem 3688
Chemical data
Formula C8H9ClN2O2S 
Mol. mass 232.68726 g/mol
SMILES eMolecules & PubChem
Synonyms IDRA-21
Therapeutic considerations
Pregnancy cat.  ?
Legal status Investigational New Medicine

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]


  1. ^ Uzunov, DP; Zivkovich; Pirkle; Costa; Guidotti (Aug 1995). "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. 
  2. ^ Thompson, DM; Guidotti; Dibella; Costa (Aug 1995). "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. 
  3. ^ Zivkovic, I; Thompson; Bertolino; Uzunov; Dibella; Costa; Guidotti (Jan 1995). "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. 
  4. ^ Buccafusco, JJ; Weiser; Winter; Klinder; Terry (Jan 2004). "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. 
  5. ^ Arai, A; Guidotti; Costa; Lynch (Sep 1996). "Effect of the AMPA receptor modulator IDRA 21 on LTP in hippocampal slices". Neuroreport 7 (13): 2211–5. ISSN 0959-4965. PMID 8930991. 
  6. ^ 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. 
  7. ^ Yamada, KA; Covey; Hsu; Hu; Hu; He (May 1998). "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. 
  8. ^ Nagarajan, N; Quast; Boxall; Shahid; Rosenmund (Nov 2001). "Mechanism and impact of allosteric AMPA receptor modulation by the ampakine CX546". Neuropharmacology 41 (6): 650–63. ISSN 0028-3908. PMID 11640919. 
  9. ^ Phillips, D; Sonnenberg; Arai; Vaswani; Krutzik; Kleisli; Kessler; Granger et al. (May 2002). "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. 
  10. ^ 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. 
  11. ^ Black, MD (Apr 2005). "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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