The Full Wiki

More info on IDRA-21

IDRA-21: Wikis

Advertisements

Note: Many of our articles have direct quotes from sources you can cite, within the Wikipedia article! This article doesn't yet, but we're working on it! See more info or our list of citable articles.

Encyclopedia

From Wikipedia, the free encyclopedia

IDRA-21
Systematic (IUPAC) name
7-chloro-3-methyl-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide
Identifiers
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]

References

  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. http://www.pnas.org/cgi/pmidlookup?view=long&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. http://molpharm.aspetjournals.org/cgi/pmidlookup?view=long&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. 
Advertisements

Advertisements






Got something to say? Make a comment.
Your name
Your email address
Message